Influence of oceanography on bowhead whale (Balaena mysticetus) foraging in the Chukchi Sea as inferred from animal-borne instrumentation

17 USC 105 interim-entered record; under review.The article of record as published may be found at https://doi.org/10.1016/j.csr.2021.104434The distribution of the Bering-Chukchi-Beaufort Sea population of bowhead whales (Balaena mysticetus) is largely centered in the Chukchi Sea in autumn (September–November), which is also when sea ice is at minimum extent allowing for increased ship traffic and industrial activity. Prior work paired autumn movements of bowhead whales in the Chukchi Sea with simulated hydrographic information and concluded whales followed relatively cold, saline waters of Pacific origin during migration (<0 ◦C, 31.5–34.25 psu). We attached six Satellite Relay Data Logger (SRDLs) that included miniaturized Conductivity, Temperature, and Depth (CTD) sensors capable of collecting temperature (T) and salinity (S) profiles as whales dove, allowing us to verify and expand upon prior habitat studies. Areas where transiting whales stopped and lingered (presumably to feed) were associated with colder surface temperatures and lingering behavior peaked where seafloor salinity was ~33 psu. Whales were also more likely to linger in areas where density gradients were lower at the seafloor. Whales targeted colder, more saline waters of Pacific origin, in agreement with our prior work. Surface and dive behavior of whales tagged in this and other studies suggests that most feeding in the central Chukchi Sea is occurring at depths below the surface, and that surface temperature is indicative of (a proxy for) other processes occurring at depth. We suggest that colder surface temperatures are indicative of the main pathway(s) by which zooplankton are advected through the Chukchi Sea. However, because similar movement patterns in other stocks of bowhead whales have been interpreted as the avoidance of thermal stress, we suggest more research is needed on thermoregulation before this question can be resolved.Global Model Analysis programDepartment of Energy RegionalOffice of Naval Research Arctic and Global Prediction programNational Science Foundation Arctic System Science progra

Use of the Alaskan Beaufort Sea by Bowhead Whales (Balaena mysticetus) Tagged with Satellite Transmitters, 2006 – 18

We used satellite telemetry to examine bowhead whale movement behavior, residence times, and dive behavior&nbsp;in the Alaskan Beaufort Sea, 2006 – 18. We explored the timing and duration of use of three subregions (western, central, eastern) within the Alaskan Beaufort Sea and applied a two-state switching state-space model to infer bowhead whale behavior state as either transiting or lingering. Transiting whales made direct movements whereas lingering whales changed direction frequently and were presumably feeding. In spring, whales migrated across the Alaskan Beaufort Sea in 7.17 ± 0.41 days, primarily off the continental shelf over deep water. During the autumn migration, whales spent over twice as much time crossing the Alaskan Beaufort Sea than in spring, averaging 18.66 ± 2.30 days, spending 10.05 ± 1.22 days in the western subregion near Point Barrow. Most whales remained on the shelf during the autumn migration and frequently dove to the seafloor, where they spent 45% of their time regardless of behavioral state. Consistent dive behavior in autumn suggests that the whales were looking for food while migrating, and the identification of lingering locations likely reflects feeding. The lack of lingering locations in the eastern and central subregions suggests that prey densities are rarely sufficient to warrant whales pausing their migration for multiple days, unlike in the western subregion near Point Barrow, where bowhead whales regularly&nbsp;lingered for long periods of time.À l’aide de la télémétrie satellitaire, nous avons examiné les comportements de déplacement des baleines boréales,&nbsp;leurs temps de séjour et leurs comportements de plongée dans les eaux alaskiennes de la mer de Beaufort entre 2006 et 2018. Nous avons exploré le moment et la durée d’utilisation de trois sous-régions (ouest, centre et est) des eaux alaskiennes de la mer de Beaufort et appliqué un modèle à changement binaire espace-état afin de déduire l’état du comportement des baleines boréales comme étant soit en mode transit, soit en mode flânerie. Les baleines en mode transit se déplaçaient de manière directe, tandis que celles en mode flânerie changeaient souvent de direction et étaient probablement en train de se nourrir. Au printemps, les baleines migraient dans les eaux alaskiennes de la mer de Beaufort en 7,17 ± 0,41 jours, principalement au large du plateau continental, dans les profondeurs. Durant la migration automnale, les baleines passaient plus de deux fois plus de temps à traverser les eaux alaskiennes de la mer de Beaufort qu’au printemps, en moyenne 18,66 ± 2,30 jours, passant 10,05 ± 1,22 jours dans la sous-région de l’ouest, près de Point Barrow. Pendant la migration automnale, la plupart des baleines restaient dans le plateau continental et plongeaient souvent jusqu’au plancher océanique, où elles passaient 45 % de leur temps, peu importe leur état de comportement. À l’automne, le comportement de plongée régulier suggère que les baleines étaient à la recherche de nourriture pendant leur migration, et les lieux où elles flânaient étaient vraisemblablement indicateurs d’un mode d’alimentation. L’absence de lieux de flânerie dans les sous-régions de l’est et du centre suggère que la densité des proies est rarement suffisante pour que les baleines justifient d’interrompre leur migration pendant plusieurs jours, contrairement à la sous-région de l’ouest, près de Point Barrow, où les baleines boréales flânaient régulièrement pendant de longues périodes

Global analyses of human immune variation reveal baseline predictors of postvaccination responses.

A major goal of systems biology is the development of models that accurately predict responses to perturbation. Constructing such models requires the collection of dense measurements of system states, yet transformation of data into predictive constructs remains a challenge. To begin to model human immunity, we analyzed immune parameters in depth both at baseline and in response to influenza vaccination. Peripheral blood mononuclear cell transcriptomes, serum titers, cell subpopulation frequencies, and B cell responses were assessed in 63 individuals before and after vaccination and were used to develop a systematic framework to dissect inter- and intra-individual variation and build predictive models of postvaccination antibody responses. Strikingly, independent of age and pre-existing antibody titers, accurate models could be constructed using pre-perturbation cell populations alone, which were validated using independent baseline time points. Most of the parameters contributing to prediction delineated temporally stable baseline differences across individuals, raising the prospect of immune monitoring before intervention

Damaged DNA Binding Protein 2 Plays a Role in Breast Cancer Cell Growth

The Damaged DNA binding protein 2 (DDB2), is involved in nucleotide excision repair as well as in other biological processes in normal cells, including transcription and cell cycle regulation. Loss of DDB2 function may be related to tumor susceptibility. However, hypothesis of this study was that DDB2 could play a role in breast cancer cell growth, resulting in its well known interaction with the proliferative marker E2F1 in breast neoplasia. DDB2 gene was overexpressed in estrogen receptor (ER)-positive (MCF-7 and T47D), but not in ER-negative breast cancer (MDA-MB231 and SKBR3) or normal mammary epithelial cell lines. In addition, DDB2 expression was significantly (3.0-fold) higher in ER-positive than in ER-negative tumor samples (P = 0.0208) from 16 patients with breast carcinoma. Knockdown of DDB2 by small interfering RNA in MCF-7 cells caused a decrease in cancer cell growth and colony formation. Inversely, introduction of the DDB2 gene into MDA-MB231 cells stimulated growth and colony formation. Cell cycle distribution and 5 Bromodeoxyuridine incorporation by flow cytometry analysis showed that the growth-inhibiting effect of DDB2 knockdown was the consequence of a delayed G1/S transition and a slowed progression through the S phase of MCF-7 cells. These results were supported by a strong decrease in the expression of S phase markers (Proliferating Cell Nuclear Antigen, cyclin E and dihydrofolate reductase). These findings demonstrate for the first time that DDB2 can play a role as oncogene and may become a promising candidate as a predictive marker in breast cancer

IPSS-independent prognostic value of plasma CXCL10, IL-7 and IL-6 levels in myelodysplastic syndromes

Recent studies suggest a powerful prognostic value for plasma cytokine levels in primary myelofibrosis (interleukin (IL)-2R, IL-8, IL-12, IL-15 and C–X–C motif chemokine 10 (CXCL10)) and large-cell lymphoma (IL-2R, IL-8, IL-10, IL-12, CXCL9 and CXCL10). To examine the possibility of a similar phenomenon in myelodysplastic syndromes (MDS), we used multiplex enzyme-linked immunosorbent assay to measure 30 plasma cytokines in 78 patients with primary MDS. Compared with normal controls (n=35), the levels of 19 cytokines were significantly altered. Multivariable analysis identified increased levels of CXCL10 (P<0.01), IL-7 (P=0.02) and IL-6 (P=0.07) as predictors of shortened survival; the survival association remained significant when the Cox model was adjusted for the International Prognostic Scoring System, age, transfusion-need or thrombocytopenia. MDS patients with normal plasma levels of CXCL10, IL-7 and IL-6 lived significantly longer (median survival 76 months) than those with elevated levels of at least one of the three cytokines (median survival 25 months) (P<0.01). Increased levels of IL-6 were associated with inferior leukemia-free survival, independent of other prognostic factors (P=0.01). Comparison of plasma cytokines between MDS (n=78) and primary myelofibrosis (n=127) revealed a significantly different pattern of abnormalities. These observations reinforce the concept of distinct and prognostically relevant plasma cytokine signatures in hematological malignancies

Liver Fluke Induces Cholangiocarcinoma

The authors discuss the molecular pathogenesis of opisthorchiasis and associated cholangiocarcinogenesis, particularly nitrative and oxidative DNA damage and the clinical manifestations of cholangiocarcinoma

The associated expression of Maspin and Bax proteins as a potential prognostic factor in intrahepatic cholangiocarcinoma

BACKGROUND: Maspin, a member of the serpin family, is a suppressor of tumor growth, an inhibitor of angiogenesis and an inducer of apoptosis. Maspin induces apoptosis by increasing Bax, a member of the Bcl-2 family of apoptosis-regulating proteins. In this exploratory study, we investigated the associated expression of Maspin and Bax proteins as a potential prognostic factor in intrahepatic cholangiocarcinoma (IHCCA). METHODS: Twenty-two paraffin-embedded samples were analyzed by immunohistochemical methods using Maspin, Bax and CD34 antibodies. Maspin was scored semiquantitatively (HSCORE). Apoptosis was assessed using an antibody against cleaved caspase-3. RESULTS: The strong relationship observed between the expression of Maspin and Bax, indicates that Bax is likely to be the key effector of Maspin-mediated induction of apoptosis as indicated by the activation of cleaved caspase-3. We categorized Maspin HSCORE by calculating the optimal cutpoint. A Maspin HSCORE above the cutpoint was inversely related with tumor dimension, depth of tumor and vascular invasion. Uni/multivariate analysis suggests that a Maspin HSCORE below the cutpoint significantly worsens the patients' prognosis. Tumors with Maspin HSCORE below the cutpoint had a shorter survival (11+/-5 months) than did patients with Maspin HSCORE above the cutpoint (27+/-4 months), whereas Kaplan-Meier analysis and logrank test showed no significant difference in overall survival between the patients. CONCLUSION: The associated expression of Maspin and Bax might delay tumor progression in IHCCA. Maspin above the cutpoint might counteract tumor development by increasing cell apoptosis, and by decreasing tumor mass and cell invasion. The combined expression of Maspin and Bax appears to influence the susceptibility of tumor cholangiocytes to apoptosis and thus may be involved in delaying IHCCA progression

RelB-Dependent Stromal Cells Promote T-Cell Leukemogenesis

BACKGROUND: The Rel/NF-kappaB transcription factors are often activated in solid or hematological malignancies. In most cases, NF-kappaB activation is found in malignant cells and results from activation of the canonical NF-kappaB pathway, leading to RelA and/or c-Rel activation. Recently, NF-kappaB activity in inflammatory cells infiltrating solid tumors has been shown to contribute to solid tumor initiation and progression. Noncanonical NF-kappaB activation, which leads to RelB activation, has also been reported in breast carcinoma, prostate cancer, and lymphoid leukemia. METHODOLOGY/PRINCIPAL FINDINGS: Here we report a novel role for RelB in stromal cells that promote T-cell leukemogenesis. RelB deficiency delayed leukemia onset in the TEL-JAK2 transgenic mouse model of human T acute lymphoblastic leukemia. Bone marrow chimeric mouse experiments showed that RelB is not required in the hematopoietic compartment. In contrast, RelB plays a role in radio-resistant stromal cells to accelerate leukemia onset and increase disease severity. CONCLUSIONS/SIGNIFICANCE: The present results are the first to uncover a role for RelB in the crosstalk between non-hematopoietic stromal cells and leukemic cells. Thus, besides its previously reported role intrinsic to specific cancer cells, the noncanonical NF-kappaB pathway may also play a pro-oncogenic role in cancer microenvironmental cells