Commercial fisheries have increased in all the world’s oceans with diverse unintended impacts on marine ecosystems. As a result of resource overlap, interactions between cetaceans and fisheries are a common occurrence and, in many cases, can give rise to significant conservation issues. Research on the distribution and types of such interactions is important for efficient management. In this study, we describe the behaviors of two whale species: sperm whales (Physeter macrocephalus) and northern bottlenose whales (Hyperoodon ampullatus), interacting with benthic trawlers fishing off the eastern Grand Banks of the western North Atlantic in 2007. Whale interactions were only observed when vessels were targeting Greenland halibut (Reinhardtius hippoglossoides) in deep-water fishing areas and were most common during net hauling. Sperm whales and northern bottlenose whales appeared to engage in feeding behavior close to the surface during hauling, especially during the latter stages, suggesting they targeted fish escapees rather than discards. Using photo-identification methods, seven individual sperm whales were identified with multiple resights of six individuals being recorded over an almost two month period. The maximum distance between two resights was 234 km, suggesting individual sperm whales were repeatedly targeting and even following fishing vessels over multiple days and between fishing areas. By contrast, there were no photographic resights of individual northern bottlenose whales within this study, or with substantial photo-identification catalogues from other adjacent high density areas, suggesting that individuals of this species may be less likely to follow vessels or move between areas. This study documents the earliest confirmed records of northern bottlenose whales in this remote region. These interactions and high encounter rates may indicate that adjacent populations are recovering from the previous century of commercial whaling. Our study provides new insights and details on whale-fisheries interactions, which can inform future research and help managers understand the real and perceived impacts of depredation behaviour on fisheries and whales.

Shwachman-Diamond syndrome (SDS) is characterized by exocrine pancreatic insufficiency, neutropenia, and skeletal abnormalities. Biallelic mutations in SBDS , which encodes a ribosome maturation factor, are found in 90% of SDS cases. Sbds ^–/– mice are embryonic lethal. Using CRISPR/Cas9 editing, we created sbds- deficient zebrafish strains. Sbds protein levels progressively decreased and became undetectable at 10 days postfertilization (dpf). Polysome analysis revealed decreased 80S ribosomes. Homozygous mutant fish developed normally until 15 dpf. Mutant fish subsequently had stunted growth and showed signs of atrophy in pancreas, liver, and intestine. In addition, neutropenia occurred by 5 dpf. Upregulation of tp53 mRNA did not occur until 10 dpf, and inhibition of proliferation correlated with death by 21 dpf. Transcriptome analysis showed tp53 activation through upregulation of genes involved in cell cycle arrest, cdkn1a and ccng1 , and apoptosis, puma and mdm2 . However, elimination of Tp53 function did not prevent lethality. Because of growth retardation and atrophy of intestinal epithelia, we studied the effects of starvation on WT fish. Starved WT fish showed intestinal atrophy, zymogen granule loss, and tp53 upregulation — similar to the mutant phenotype. In addition, there was reduction in neutral lipid storage and ribosomal protein amount, similar to the mutant phenotype. Thus, loss of Sbds in zebrafish phenocopies much of the human disease and is associated with growth arrest and tissue atrophy, particularly of the gastrointestinal system, at the larval stage. A variety of stress responses, some associated with Tp53, contribute to pathophysiology of SDS.

Shwachman-Diamond syndrome (SDS) is characterized by neutropenia, exocrine pancreatic insufficiency, and bony abnormalities with an increased risk of myeloid neoplasia. Almost all cases of SDS result from biallelic mutations in Shwachman-Bodian-Diamond syndrome (SBDS). SBDS interacts with elongation factor–like 1 (EFL1) to displace eukaryotic initiation factor 6 (EIF6) from the 60S ribosomal subunit. Released EIF6 permits the assembly of ribosomal large and small subunits in the cytoplasm. Decreased EIF6 levels due to haploinsufficiency or missense mutations, which lead to decreased protein expression, may provide a somatic genetic rescue and antileukemic effects. We observed accumulation of EIF6 protein in sbds -KO zebrafish models, confirmed this accumulation in patient-derived tissues, and correlated these with changes in ribosomal proteins and tumor protein p53 (TP53) pathways. The mechanism of action for this adaptive response is unknown. To address this, we generated eif6 -KO zebrafish, which do not survive more than 10 days after fertilization. We also created 2 mutants with low Eif6 expression, i.e., 5%–25% of WT levels, that could survive until adulthood. We bred them with sbds -null strains and analyzed their phenotype and biochemical properties. Low Eif6 levels reduced Tp53 pathway activation but did not rescue neutropenia in Sbds-deficient zebrafish. Further studies elucidating the interplay between SBDS, EIF6, and TP53 and cellular stress responses offer promising insights into SDS pathogenesis, somatic genetic rescue, and therapeutic strategies.

Defects in ribosomal biogenesis profoundly affect organismal development and cellular function, and these ribosomopathies produce a variety of phenotypes. One ribosomopathy, Shwachman–Diamond syndrome (SDS) is characterized by neutropenia, pancreatic exocrine insufficiency, and skeletal anomalies. SDS results from biallelic mutations inSBDS, which encodes a ribosome assembly factor. Some individuals express a missense mutation,SBDS^R126T, along with the common K62X mutation. We reported that thesbds-null zebrafish phenocopies much of SDS. We further showed activation of Tp53-dependent pathways before the fish died during the larval stage. Here, we expressedSBDS^R126Tas a transgene in thesbds^−/−background. We showed that one copy of theSBDS^R126Ttransgene permitted the establishment of maternal zygoticsbds-null fish which produced defective embryos withcdkn1aup-regulation, a Tp53 target involved in cell cycle arrest. None survived beyond 3 dpf. However, two copies of the transgene resulted in normal development and lifespan. Surprisingly, neutropenia persisted. The surviving fish displayed suppression of female sex differentiation, a stress response in zebrafish. To evaluate the role of Tp53 in the pathogenesis ofsbds^−/−fish phenotype, we bred the fish with a DNA binding deficient allele,tp53^M214K. Expression of the loss-of-functiontp53^M214Kdid not rescue neutropenia or survival insbds-null zebrafish. Increased expression ofcdkn1awas abrogated in thetp53^M214K/M214K;sbds^−/−fish. We conclude that the amount of SBDS^R126Tprotein is important for development, inactivation of Tp53 fails to rescue neutropenia or survival in thesbds-null background, andcdkn1aup-regulation was dependent on WTtp53. We hypothesize that additional pathways are involved in the pathophysiology of SDS.

Commercial fisheries have increased in all the world’s oceans with diverse unintended impacts on marine ecosystems. As a result of resource overlap, interactions between cetaceans and fisheries are a common occurrence and, in many cases, these give rise to significant conservation issues. Research on the distribution and types of such interactions is important for efficient management. In this study, we describe the behaviors of two whale species: sperm whales ( Physeter macrocephalus ) and northern bottlenose whales ( Hyperoodon ampullatus ), interacting with benthic trawlers fishing off the eastern Grand Banks of the western North Atlantic in 2007. Whale interactions were only observed when vessels were targeting Greenland halibut ( Reinnhardtius hippoglossoides ) in deep-water fishing areas and were most common during net hauling. Sperm whales and northern bottlenose whales appeared to engage in feeding behavior close to the surface during hauling, especially during the latter stages, suggesting they targeted fish escapees rather than discards. Using photo-identification methods, seven individual sperm whales were identified with multiple resights of six individuals being recorded over an almost two month period. The maximum distance between two resights was 234 km, suggesting individual sperm whales were repeatedly targeting and even following fishing vessels over multiple days and between fishing areas. By contrast, there were no photographic resights of individual northern bottlenose whales within this study, or with substantial photo-identification catalogues from other adjacent high density areas, suggesting that individuals of this species may be less likely to follow vessels or move between areas. This study documents the earliest confirmed records of northern bottlenose whales in this remote region. These interactions and high encounter rates may indicate that adjacent populations are recovering from the previous century of commercial whaling. Our study provides new insights and details on whale-fisheries interactions, which can inform future research and help managers understand the real and perceived impacts on fisheries and whales.