Memory B cells and long-lived plasma cells are key elements of adaptive humoral immunity. Regardless of the immunoglobulin class produced, these cells can ensure long-lasting protection but also long-lasting immunopathology, thus requiring tight regulation of their generation and survival. Among all antibody classes, this is especially true for IgE, which stands as the most potent, and can trigger dramatic inflammatory reactions even when present in minute amounts. IgE responses and memory crucially protect against parasites and toxic components of venoms, conferring selective advantages and explaining their conservation in all mammalian species despite a parallel broad spectrum of IgE-mediated immunopathology. Long-term memory of sensitization and anaphylactic responses to allergens constitute the dark side of IgE responses, which can trigger multiple acute or chronic pathologic manifestations, some punctuated with life-threatening events. This Janus face of the IgE response and memory, both necessary and potentially dangerous, thus obviously deserves the most elaborated self-control schemes. IgE was the last discovered Ig class  selection and production, the development of which implies several phases. The first is antigen (Ag) independent, with V(D)J assembly creating functional B cell receptor (BCR) genes. In a second phase after cells have reached the periphery, Ag activation can induce expression of activation-induced deaminase (AID) , 2, thenIg class , 5, notaBoth IgE and IgG emerged in proto-mammals from the ancestral reptilian IgY molecule and further diverged . IgG andIgE antibodies are notably active against helminths, in responses featuring high total and specific IgE levels, hyper-eosinophilia and Th2 polarization . IgE havREG cells, and dendritic cells dampen IgE responses  donor and acceptor regions Figure . S regioI promoters are crucial CSR regulators for each isotype by carrying sites for specific transcription factors. The Iε promoter binds E2A, AP1, C/EBP, STAT6, PU.1, Pax5, and NF-κB , 29. Cla1  . Consist1 .1 intermediate  or sequential (Sμ to Sγ1 first and then to Sε) with an IgGrmediate   and two membrane exons M1 and M2), while PCs produce secreted transcripts lacking membrane exons  site downstream of membrane exons. Maturation of these mRNAs then relies on suboptimal variant polyA sites likely lowers mIgE expression. The resulting ratio of secreted-type/membrane-type ε mRNA is indeed higher than for IgG in stimulated B cells, but partially normalized upon insertion of a classical polyA site downstream the IgE membrane exons in vitro . However into Cε, Figure in vivo in spleen and bone marrow . Convergent data now show that the rate-limiting step of IgE PC generation is a specifically fragile and short-lived status of mIgE+ lymphocytes. Poorly moving and briefly surviving, these mandatory precursors  of membrane exons  monoclonal antibody (MAb)  . Anti-hue Figure , or humae Figure . Solubleotal IgE . Anotherotal IgE . It remaotal IgE , 75. AltPhage display helped identify two mIgE intra-cytosolic binding proteins: HPK1 binds mIgE and other isotype tails  while HAin vitro in cell lines, both human mIgE forms expressed into the immature WEHI cell line, associated with mouse signaling co-receptors Igα/Igβ, and inhibited cell growth after mSIgE BCR cross-linking  and homologous (human mature B cell line) transfectants. Consistently, we observed increased apoptosis of mIgEaffected . Anotherg defect .in vivo complexity of IgE responses. Beyond these intrinsic aspects, extracellular factors such as cell–cell interactions, Ag presentation by B-cells to T-cells and various soluble factors could strongly influence IgE+ B cell fate. Methods and mouse models have been developed by different labs and help further understand IgE responses.All these data are informative about the B-cell intrinsic impact of mIgE expression but do not integrate the + cells  KI downstream of Cε -infected WT mice, IgE+ PCs were localized outside GC, whereas IgE CSR occurred in GC IgG1+ cells, i.e., through sequential CSR  IgE, whereas direct IgE CSR generates low-affinity IgE   . We can ceptors) , as wellceptors) . The spephocytes .+ cells in vivo. The first one (M1’ GFP) includes a human EMPD IgE domain knocked into the mouse Cε . A second model used the peptide 2A system to really tag IgE+ cells, coupling translation of mIgE and the fluorescent protein “Venus” , recruiting adaptor or signaling proteins , or through still unknown interactions. TM and extra-membrane domains notably contribute to specific interactions with Ig-α, CD19 and probably other molecules. IgE is highly flexible , 104 andA new mouse model has been generated to force membrane IgE expression from early B cell development , similar+ memory B cells. It is interesting to note that upon all different KI strategies deployed to investigate IgE+ cells in vivo . Acting on the true memory cells responsible for the long-term infusion of IgE should by contrast rather focus onto IgE PCs.Membrane IgE expression BL and MC wrote the manuscript, OD created the figures and participated to the redaction, and ZD helped for references and redaction.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Type VI collagen is supposed to be a regulation factor in adipogenesis. This study aimed to assess the promoting effect of vitamin C (VC) on adipogenic differentiation of preadipocytes as well as its mechanism.Five sets of different combinations of chemicals were used to inhibit synthesis of type I to VI collagens, blocking ERK1/2 phosphorylation during adipogenesis of 3T3-L1 preadipocytes. Furthermore, to explore whether collagen VI plays a critical role during adipogenesis, specific knockdown of collagen VI was performed by using RNA interference. The morphology and expression patterns of several target factors involved in adipogenesis were assessed at various time points.MEK1 and MEK2 and a type of MAPK/ERK kinase, up-regulated the expression of collagen VI, while it down-regulated the adipogenic-specific factors.A reduction in ERK1/2 phosphorylation and an increase in collagen VI and adipogenic-specific factors, such as C/EBPβ, PPARγ and C/EBPα, were observed after treating adipogenic 3T3-L1 cells with AA2P, a stable derivative of VC. Inhibition of collagen synthesis by ethyl-3, 4-dihydroxybenzoate (EDHB) or by specific knockdown of collagen VI by RNAi could promote ERK1/2 phosphorylation. The ERK1/2 phosphorylation in both cases could be attenuated by AA2P treatment. In addition, the inhibition of ERK1/2 phosphorylation by U0126, a highly selective inhibitor of both AA2P could up-regulate the expression of collagen VI by attenuating ERK1/2 phosphorylation, further up-regulating adipocyte-specific factors, thus finally promoting the adipogenesis of 3T3-L1 preadipocytes.The online version of this article (10.1186/s12986-017-0234-y) contains supplementary material, which is available to authorized users. In addition to significant increases in protein expression directly related to lipid metabolism, the type and level of ECM components secreted during adipogenesis also change , 2. It hCollagen VI is comprises the three subunits of α1, α2 and α3, which are encoded by different genes. The silencing of the Col6α1 gene can prevent the secretion and assembly of collagen VI in the ECM, affecting its function . CompareEthyl-3, 4-dihydroxybenzoate (EDHB) is a known ideal inhibitor through which we can explore the role of collagens in regulating adipogenesis of preadipocytes . It inhiIn addition to its antioxidant activity, vitamin C (VC) acts as a cofactor of the hydroxylating enzyme of proline and lysine residues in procollagen, which stabilizes the collagen triple helix. Moreover, VC regulates collagen synthesis, cell growth, and cell differentiation , 13. It Extracellular signal-regulated kinase (ERK) is a member of the MAPK family, which controls cell proliferation, differentiation and stress response . The ERKThere is also a link between VC and ERK. It has been reported that AA2P promotes the production of ECM components by attenuating the phosphorylation of ERK1/2 and enhances the stemness of adipose-derived stem cells and the cell sheet formation, while it has no effect on the subsequent adipogenic differentiation . In otheAA2P, EDHB and U0126 were purchased from Sigma-Aldrich . AA2P was initially dissolved in Dulbecco’s modified Eagle’s medium  in a 250 mM. EDHB was initially dissolved in absolute ethanol in a 100 mM. U0126 was initially dissolved in dimethyl sulfoxidein (DMSO) in a 100 mM. The final ethanol and DMSO concentration of the controls were adjusted to 0.1%.To produce mature adipocytes, 3T3-L1 preadipocytes  were seeded on 12-well plates with growth medium to let the cells reach 100% confluence. Two days later, the cells were induced to become mature adipocytes with a cocktail adipogenic inducers, defined as day 0 (D0) for 2 days. Next, the cells were refreshed with the maintenance medium for an additional 2 days. The medium was finally replaced with growth medium for 10 more days. The cells were treated with relative chemicals from days 0 to 14 as follows: the non-induction group (N.I.); the AA2P alone treated group (N.I. + AA2P); the adipogenic group (I), 250 μM AA2P group (I + AA2P); the 100 μM EDHB group (I + EDHB); the 100 μM EDHB plus 250 μM AA2P group (I + EDHB + AA2P); the RNAi groups; the 100 μM U0126 group (I + U0126); and the 100 μM U0126 plus 250 μM AA2P group (I + U0126 + AA2P). The experimental groups were shown in Fig. Small hairpin RNA (shRNA) of the mouse collagen VI α1 subunit lentivirus gene transfer vector encoding the GFP sequence was designed. Different siRNAs were screened by co-transfection with mouse collagen VI α1 subunit cDNA plasmid into HEK293T cells with Lipofectamine 2000 . The optimal sequence of the siRNA against the mouse collagen VI α1 subunit (5’-ACCTATTCCGTGTACCAAA-3′) (GenBank gi: NM_009933), was then cloned into the plasmid GV 112, which encodes an HIV-derived lentiviral vector containing a multiple cloning site for insertion of the shRNA constructs to be driven by an upstream U6 promoter and a downstream cytomegalovirus promoter with GFP. The resulting lentiviral vector containing mouse collagen VI α1 subunit shRNA was named Lenti-ColVI-GFP, and its sequence was confirmed by PCR and sequencing analysis. A negative control (NC) lentiviral vector (Lenti-GFP) containing NC shRNA was constructed by a similar process .3T3-L1 preadipocytes were plated in 12-well plates overnight and infected with Lenti-ColVI-GFP by addition of lentivirus diluted into 0.5 ml of Dulbecco’s modified eagle medium (DMEM) containing 5% NBCS and polybrene at an MOI of approximately 100 for 12 h at 37 °C. The medium was then replaced with growth medium until it reached 100% confluence. Adipogenic induction was initiated after 48 h of confluence. The controls were infected with NC lentivirus (I + Lenti-GFP).The cells were stained with Oil Red O (Sigma-Aldrich) at the D3, D7 and D14 after induction for determining the degree of differentiation (the ratio of adipose cells). The lipid staining was quantified by extracting the dye with 100% isopropanol and measuring the absorbance at 520 nm.Total RNA was extracted from 3T3-L1 cells at the D0, D3, D7 and D14 after induction using AxyPrep Total RNA Preparation Kit  according to the manufacturer’s protocol. RNA concentration was determined by optical density at 260 nm (OD 260) using Nanodrop . Total RNA (0.3 μg) was reverse-transcribed using First Strand cDNA Synthesis Kit . The expression level of genes was assessed by quantitative RT-PCR. cDNA product (0.2 μg) was amplified by quantitative PCR with SuperReal RT-PCR PreMix (SYBR Green) kit . The results are expressed as the fold increase relative to the controls after normalizing to the β-actin gene expression levels. The sequences of the gene-specific primers used are shown in Table Total cell proteins were isolated using a lysis buffer and sonicated as previously reported . An aliqP < 0.05 was considered statistically significant and significant between groups.Data were analyzed using SPSS version 19.0 software  and two tailed in tests. Each experiment was performed in at least triplicate. The data are expressed as the mean ± SEM with GraphPad Prism 5. Differences between groups were analyzed by conducting one-way analysis of variance (ANOVA) followed by Student’s t test. *Consistent with a previous study , AA2P alP < 0.05) in both the non-induction group and the adipogenic group. However, their expression in the late stage (D8-D14) tended to be consistent, except for PPARγ2 in the adipogenic group  was gradually reduced, and there was almost no expression in the late stage of adipogenesis. In the early and middle stages of adipogenesis, ERK1/2 phosphorylation (P < 0.05) in the AA2P treatment group was significantly lower than that in the adipogenic group. These data suggest that AA2P may attenuate the ERK1/2 phosphorylation to up-regulate the expression of collagen VI and further up-regulate the expression of SREBP-1c, C/EBPβ, PPARγ2 and C/EBPα during the adipogenesis of 3T3-L1 cells. The further question is raised: is the above mechanism by which AA2P promotes the adipogenesis of 3T3-L1 cells correct?Further studies had shown that AA2P significantly up-regulated the expression of collagen VI, SREBP-1c, C/EBPβ, PPARγ2 and C/EBPα   Fig. . In contP < 0.01), and the expression trend was opposite with collagen VI  was significantly decreased after treating with AA2P, indicating that AA2P could attenuate ERK phosphorylation. These data demonstrate that AA2P may attenuate ERK phosphorylation to up-regulate the expression of collagen VI during the adipogenesis of 3T3-L1 cells. The data shows that adipogenesis was inhibited when the expression of type I to VI collagen was suppressed, and it was reversed partially when treated with AA2P, indicating that collagens play a key role during adipogenesis. Another question is raised: is collagen VI among the types of collagen that have more importance?Moreover, our results showed that EDHB could significantly increase the ERK1/2 phosphorylation   Fig. . The knoP < 0.05); therefore, the expression of PPARγ2 in the Lenti-ColVI-GFP group was significantly lower (P < 0.01) than that in the control group. The ERK1 phosphorylation was significantly down-regulated (P < 0.05) after treatment with AA2P at D3, further demonstrating that AA2P could attenuate ERK1/2 phosphorylation, especially the ERK1 phosphorylation  , was added at the overall stage of adipogenesis or after treatment with AA2P. U0126 completely inhibited the adipogenesis of 3T3-L1 cells Fig.  and inhi01) Fig. . Further01) Fig. .Fig. 5InThe above results appear to be contrary to our expected results. However, previous studies have shown that ERK1/2 phosphorylation in the early stage of adipogenesis is essential for C/EBPs and PPARγ transcription, while PPARγ is a downstream ERK1/2 molecule and the activation of ERK1/2 could phosphorylate PPARγ, leading to a reduction in its transcriptional activity, thereby inhibiting adipogenesis . MoreoveP < 0.05) after U0126 treatment, further indicating that there is an interaction between collagen VI and ERK signaling. Moreover, AA2P could regulate the expression of collagen through ERK signaling , so that we did not know how much remained after adding EDHB (I + EDHB). We specifically knocked down collagen VI, and the ratio of adipose cells was significantly higher than that of the I + EDHB group. Furthermore, the efficiency of AA2P rescuing the ratio of adipose cells in the I + Lenti-ColVI-GFP + AA2P group was significantly higher than that in the I + EDHB + AA2P group. Taken together, we found that other collagens (type I-V) also play a role in adipogenic differentiation, while collagen VI plays a major role in adipogenic differentiation of 3T3-L1 preadipocytes.Nakajima , 2 showeTo further verify the regulation of collagen VI on the adipogenesis of 3T3-L1 cells, we used RNAi to knockdown the α1 subunit of collagen VI, which significantly inhibited adipogenesis of 3T3-L1 cells by down-regulating the expression of SREBP-1c, C/EBPβ, C/EBPα and PPARγ. However, after treating with AA2P, the adipocyte-specific factors and adipogenesis were restored partially. Moreover, the ratio of adipose cells in the Lenti-ColVI-GFP group was higher than that in the EDHB + AA2P group, indicating that AA2P promoted the expression of adipocyte specific factors by up-regulating the synthesis of the collagen VI.It has been reported that VC could up-regulate the expression of collagen I and III by inhibiting the phosphorylation of ERK1/2 , 33–37. After treating the 3T3-L1 cells with EDHB, the expression trend of the collagen VI was opposite that of the ERK1/2 phosphorylation. In other words, the ERK1/2 phosphorylation was inhibited by the expression of collagen VI. Further studies showed that the ERK1/2 phosphorylation was significantly up-regulated after knockdown of collagen VI. ERK1/2 phosphorylation was decreased after treating with AA2P, while it was significantly higher than that of the Lenti-GFP control group. Bost et al.  reportedTo further verify the role of ERK signaling, we treated the cells with U0126, an inhibitor of ERK1/2 phosphorylation, during 3T3-L1 cells adipogenesis. Previous studies have shown that the ERK1/2 phosphorylation in the early stage of adipogenesis is essential for C/EBPs and PPARγ transcription, but PPARγ is a downstream molecule of ERK1/2 and ERK1/2 phosphorylation could phosphorylate PPARγ. As result reduce in its transcriptional activity, thereby inhibiting adipogenesis , 39. TheIn this study, we have shown the significantly up-regulated expression of collagen VI after completely inhibiting ERK1/2 phosphorylation by U0126. On the contrary, the adipocyte specific gene factors were significantly down-regulated. This seems to be contrary to our hypothesis. However, AA2P only attenuates ERK1/2 phosphorylation, rather than completely inhibiting it, such as in U0126. In addition, it was surprising that the expression of SREBP-1c was not inhibited by U0126 in the early and middle stage of adipogenesis. However, it was inhibited in the late stage of adipogenesis. This issue needs to be further studied.Inhibition of ERK1/2 with U0126 results in the inhibition of adipogenesis, which is rescued by AA2P. This is puzzling since the p-ERK1/2 levels tended to decrease with increased adipogenesis.Previous studies have shown that ERK1/2 phosphorylation in the mitotic clonal expansion stage of adipogenesis is essential for C/EBPβ, while PPARγ is a downstream molecule of ERK1/2, and the activation of ERK1/2 could phosphorylate PPARγ; therefore, the p-ERK1/2 levels tended to decrease with increased adipogenesis , 39. TheOur results showed that AA2P promotes the adipogenesis of the 3T3-L1 cells by attenuating ERK signaling to up-regulate collagen VI. In the absence of p-ERK1/2, AA2P could still partially rescue the inhibitory effect of U1026 on the adipogenic differentiation of 3T3-L1 preadipocytes. The possible reason for this is that AA2P could promote the adipogenic differentiation of preadipocytes by other pathways.VC has an important epigenetic regulatory function. Yin et al.  have shoOur data indicated that AA2P promotes 3T3-L1 preadipocyte adipogenic differentiation. The speculative mechanism of effects of AA2P on cell adipogenesis is as follows: VC promoted the synthesis and secretion of collagen VI as the hydroxyl factor co-enzyme and down-regulated the ERK1/2 phosphorylation to promote the adipogenesis of the preadipocytes by up-regulating the expression of adipocyte-specific factors, such as SREBP-1c, C/EBPβ, PPARγ and C/EBPα; AA2P up-regulated the expression of collagen VI by attenuating ERK1/2 phosphorylation, further up-regulating adipocyte-specific factors, and finally promoting the adipogenesis of 3T3-L1 cells Fig. . It is nAdditional file 1:a 5 × 104 3T3-L1 preadipocytes/ml were plated in 12-well plates overnight and infected with Lenti-ColVI-GFP lentivirus by addition of lentivirus diluted into 0.5 ml of Dulbecco’s modified eagle medium (DMEM) containing 5% NBCS and polybrene at the MOI of 0, 20, 50 and 100 for 12 h at 37 °C. The medium was then replaced with growth medium until it reached 100% confluence. Adipogenic induction was initiated after 48 h of confluence. The controls were infected with NC lentivirus (I + Lenti-GFP); b After screening out the optimal MOI value of the lentivirus, we detected the knockdown efficiency of Col VI using real-time quantitative reverse transcription. Values are expressed as the mean ± SEM. **P < 0.01 versus the control group (n = 3). (PDF 234 kb)Screened the MOI value of the lentivirus and detected the knockdown efficiency of Col VI: Additional file 2:P < 0.05 versus the control group (n = 3). (PDF 1599 kb)The effect of AA2P on adipogenesis is dose-dependent: a 3T3-L1 preadipocytes were seeded on 12-well plate with growth medium , streptomycin (100 mg/mL) and 2 mM L-glutamine) to let the cells reached 100% confluent. Two days later, the cells were induced for mature adipocytes with cocktail adipogenic induction medium (growth medium supplemented with 1.7 μM insulin) for an additional 2 days. The medium was finally replaced with growth medium for 10 more days. AA2P was added from the D0 to D14 at final concentrations of 0, 100, 250 and 500 μM, respectively; b On day 14, the cells were stained with Oil red O; The lipid the staining was quantified by extracting the dye with 100% isopropanol and measuring the absorbance at 520 nm. Values are expressed as the mean ± SEM. *


Three GPS trackers have been deployed on sea ice in Fram Strait collecting GPS positions between 7th July 2016 until 10th September 2016 with an interval between 5 and 30 min. For an easy understanding and usage, corresponding satellite images and python scripts are added to the GPS data. Specifications TableValue of the data●The data can be used to gain a better understanding of short-term sea ice drift variability and to investigate ice drift on a high temporal resolution.●The data allows to validate sea ice drift algorithms in Fram Strait and can potentially show how displacements from subsequent satellite images relate to instantaneous sea ice velocity.●The attached python scripts can be used to work with other GPS buoy data.1Fram Strait represents a major gateway between the Arctic Ocean and the Atlantic Ocean, both in terms of oceanic heat transport into the Arctic and sea ice export into lower latitudes. About 10% of the Arctic sea ice cover is exported through Fram Strait every year GPS trackers have been deployed on wooden constructions on loose ice floes and pack-ice in Western Fram Strait during the UNDER-ICE cruise of KV Svalbard in July 2016.A total of three GPS trackers  have been deployed on sea ice between 7th and 8th July 2016, collecting GPS data until 10th September 2016 with an interval between 5 and 30 min. For further technical specifications about the trackers see the user manual from Xeos Technologies Table of GPS trackers2Three wooden constructions were built including a heavy metal chain on the lower end to prevent tipping over . The wooTo provide a good overview of the sea ice situation around the GPS trackers, optical satellite images from MODIS, Landsat-8 and Sentinel-2 were collected. The positions of the three trackers are indicated on the attached satellite images using the same color coding as in the plots.http://www.geonova.no/diaries/sabvabaa/). From August 2014, Yngve Kristoffersen and Audun Tholfsen were drifting on an ice station including the hovercraft 'Sabvabaa' for 353 days over a distance of 2.200 km along the submarine Lomonosov Ridge. The hovercraft GPS data used in this document was collected between 31st August 2014 and 6th July 2015 with a temporal resolution of 10 s.To compare the collected high-resolution sea ice drift data from Fram Strait with the situation in the central Arctic, we got access to the hovercraft GPS data from the FRAM 2014/15 expedition (t, ranging from 5 min to 72 h.


Purpose. Anterior screw fixation has become a popular surgical treatment method for instable odontoid fractures. Screw loosening and migration are a rare, severe complication following anterior odontoid fixation, which can lead to esophagus perforation and requires revision operation. Methods. We report a case of screw loosening and migration after anterior odontoid fixation, which perforated the esophagus and was excreted without complications in a 78-year-old male patient. Results. A ventral dislocated anterior screw perforated through the esophagus after eight years after implantation and was excreted through the gastrointestinal (GI) tract. At a 6-month follow-up after the event the patient was asymptomatic. Conclusion. Extrusion via the GI tract is not safe enough to be considered as a treatment option for loosened screws. Some improvements could be implemented to prevent such an incident. Furthermore, this case is a fine example that recent preoperative imaging is mandatory before revision surgery for screw loosening. Odontoid fractures are the most common type of cervical spine fractures in patients older than 70 years  often reThe present case report describes a 78-year-old patient who presented with dysphagia eight years following anterior odontoid screw fixation. The odontoid screw appeared to be dislocated ventrally and passed through the gastrointestinal tract in the further course, from where it was excreted without complications.A 78-year-old man, with a history of anterior screw fixation of an odontoid type II fracture after falling from a two-meter height eight years ago , presentX-ray imaging of the symptomatic patient eight years after operation disclosed a ventral migration of the odontoid screw . SubsequWhen the patient was hospitalized in our center for revision surgery, four weeks after the migration was first diagnosed, a preoperative planning computed tomography (CT) was performed. The screw could not be detected anymore, the eight-year-old fracture gap was not consolidated, and the odontoid process was not dislocated . ImmediaProphylactic antibiotic therapy with amoxicillin/clavulanic acid for seven days was initiated when passage of the screw into the gastrointestinal system became evident. The patient was discharged after excretion of the screw, and full mobilization and gradual weaning from the foam cervical collar were advised. Surgical odontoid refixation was not considered due to the concomitant diseases as described above and lack of symptoms. At a 6-month follow-up after the event the patient was asymptomatic.In a meta-analysis of 48 studies on anterior odontoid screw fixation a random-effect pooled reoperation rate of 5% was calculated caused by heterogeneous reasons including device related reasons as screw loosening or migration and screw-pullout . Screw lThe clinical presentation of oesophageal perforation can range from asymptomatic presentation to local infection to infection of the mediastinum and death and therefore is considered a severe complication , 16. SinAccording to earlier reports of screw and plate loosening following cervical spine fusion, initial inadequate positioning or engagement of screws in a plate and local infection seems to be the main cause for this incident , 19. In We report a time delay of four weeks between the first radiologic diagnosis of screw migration and hospitalization for screw extraction. Esophageal perforation could have been avoided by rapid surgery, as suggested by other published cases of screw migration of the cervical region .Even though this incident did not lead to serious injury of the patient, we considered it a serious device caused complication worth publication. Extrusion via the GI tract is not safe enough to be considered as a treatment option; some improvements could be implemented to prevent such an incident: (1) the most important lesson to be learned from this case is that surgery for revision should be scheduled as soon as possible when screw loosening or migration appears in the neck region, to prevent potentially fatal complications. (2) The patient discontinued radiological follow-up one year after his operation, which should have been extended in synopsis with the initially not fully satisfying surgical result. Monitoring of the fracture healing using postoperative CT examination could have led to earlier intervention. (3) The present case is a fine example that recent preoperative imaging is mandatory before revision surgeries of loosen screws in the cervical spine region.


Based on skeletal examinations, facial reconstructions, genetic analyses, and stable oxygen isotope analyses, the birthplace, mobility, ancestry, pathology, and physical appearance of these people are presented. The stories are discussed within the relevant historical context. These three people would have been ordinary citizens, without any privileges out of the ordinary, which makes them quite rare in the academic literature. Through the study of individuals one gets a unique look into the Norwegian medieval society.This article presents the life stories of three individuals who lived in Trondheim, Norway, during the 13 This article will tell the stories of three individuals who ended their lives in medieval Trondheim, Norway. They may have been contemporaries, they may have known each other, or they may have been completely oblivious to each other’s existence. What is for certain is that these three people were buried in the same graveyard in Trondheim ).The remains of these people were recovered from the Library site in Trondheim which was excavated during 1984 and 1985 . There iThe Library site graveyard has, archaeologically, been divided into three burial phases  which ha18O) of the enamel on the first and the third molars as well as ancient DNA (aDNA) analysis. The skeletal remains of these people have also been examined anthropologically to determine sex, to estimate age at death and living stature, and to establish their accessible history of disease and trauma. Radiographs were taken of the tibiae to look for Harris lines to assess possible episodes of stunted growth , andee: e.g. , 14, 15)https://www.etikkom.no/en/our-work/about-us/the-national-committee-for-research-ethics-on-human-remains)The study was approved by “The national committee for research ethics on human remains”: case 2012/223  is 70 cm. For the radiographs of the tibiae an AGFA Structurix D4 Pb (48cmX10cm) film was used. The bone was placed on the film and its identity number was marked on the film with numbers made of lead. The voltage employed was 65 kV, the tube currency 4,5 mA and the exposure time 3 minutes. For the cranial radiographs, an AGFA Structurix D5 Pb (24cmX10cm) film was used. Here the voltage was 60 kV, the currency 4,5 mA and the exposure time 9 minutes.18OC) from the first (M1) and the third (M3) molars has been analysed for the three individuals. The analyses were carried out by GNS Science  and the results were reported on the V-SMOW scale. The δ18OC data was then converted to δ18Ow (oxygen composition in water/precipitation) by using equation 6 from Daux et al. [The oxygen composition in enamel apatite carbonates  and the breastfeeding effect (diminution of 0.2‰ to 1.0‰ must be applied to the δ18OC of M1) are taken into account.Breastfeeding affects the oxygen composition in the body –21 and, ed child . For det18Ow from temperature, a 1°C increase equals an increase of δ18Ow by 0.7‰. Thus, it is important to assess the average temperature at the time the examined teeth developed. For the purpose of the three individuals discussed in this paper, the exact year of birth is not known but they were most likely born during the first half of the 13th or possibly towards the end of the 12th century. The temperature reconstructions of the growing season temperature in west-central and central Scandinavia [Another variable influencing the isotope composition in precipitation is temperature. Average yearly temperatures fluctuate from one year to another and, thus, influence the isotopic composition of precipitation accordingly. Applying the formula developed by Dansgaard  for tradndinavia –26 show 18Ow for drinking water in Trondheim has been determined by Hamre and Daux [18Ow data for the rest of Europe has been gathered from GNIP  precipitation collection stations and various publications.The δand Daux  to -8.7‰Ancient DNA analyses on the human remains comprised three main laboratory processes: DNA extraction, DNA typing, and results interpretation, all performed at the Institute of Legal Medicine (GMI), Medical University of Innsbruck, Austria. The analyses were performed in a forensic molecular genetic laboratory designed and optimised to meet the required high quality. After photo documentation of the individual specimens and weighing of the received samples, work lists were generated to pursue molecular genetic analyses.2O, absolute EtOH), dried, and ground using a horizontally oscillating ballmill. Bone powder was dissolved in a hybridisation oven, the DNA extracted with a modified silica-column-based Spin Filter (SF) method [In order to avoid the possibility that DNA (modern) located on the surface of the samples could interfere with the analysis, the remains were thoroughly cleaned. The surfaces of the fragments were mechanically cleaned with sterile scalpel blades. The samples were then washed  method , 28.The total amount of nuclear (n)DNA and mitochondrial (mt)DNA present in the purified DNA extract was determined by means of a modified real-time (rt)PCR DNA quantification approach , 30. TheThe skulls were assessed and facial depictions produced by Face Lab at Liverpool John Moores University. The depiction of faces of the dead can be a useful tool for promoting recognition leading to forensic identification. Post-mortem facial depiction (otherwise known as reconstruction or approximation) is described as the interpretation of human remains in order to suggest the living appearance of an individual . It is wth and 21st centuries clinical imaging methods have been utilised to measure living subjects, starting with planar x-rays and eventually advanced 3D imaging, such as computed tomography, Magnetic Resonance Imaging, ultrasound, low dose cone-beam computed tomography and holographic topometry. There are many sets of data available from different in vivo ethnic groups across the world for use in craniofacial analysis. There are data for adults from a variety of ethnic groups in Germany, Belgium, the former Soviet Union, Slovakia, Japan, South Korea, The Netherlands, USA, Egypt, Chile, Turkey, India and South Africa. There are datasets for children from the USA, the UK, Japan and the Philippines. Collations of these datasets can be found in some publications [www.craniofacialidentification.com; www.craniofacial-id.com).In addition, tissue depth data at anatomical points across the skull are utilised to act as guidelines for the amount of soft tissue over the skull as related to sex, age and ethnic group. Throughout the 20ications , 54 and The skulls were scanned using Artec Space Spider, which is a high-resolution 3D scanner based on blue light technology. The scanner’s ability to render complex geometry, sharp edges and thin ribs means it is an ideal industrial 3D scanner for high resolution capturing of objects followed by the export of the final 3D model as an obj. file. The scan data was translated into 3D digital models of the skulls in order to produce facial depictions in our 3D computer system. The system employs Geomagic Touch X hardware and Freeform Modelling Plus software. This system has haptic feedback and allows the practitioner to feel the surface of the model that can be seen on the monitor. A database was accessed for the depiction process containing pre-modelled muscles and anatomical structures created for use in forensic reconstruction.This facial depiction system has been tested using the skulls of living subjects , 56 and The reason for selecting these three individuals was to illustrate diversity in medieval Trondheim, but the selections had to be made within some limitations and according to certain criteria. Facial reconstructions were going to be made from the remains of these individuals, for use in a museum exhibition at Bryggens Museum in Bergen, Norway. Thus, the first criterion was that the skull had to be sufficiently complete. This excluded about half of the 41 medieval skeletons which had been examined and analysed and were, therefore, potential candidates for selection. After that, isotope results were the deciding factor for choosing SK152, the mtDNA profile was important for including SK196, while the last individual, SK259, was chosen more at random with the only deciding criterion being that he was male. Other information about pathology and trauma was added later and were not factors in selection. Thus, SK152 was chosen due to her oxygen isotope values showing that she had been born a long distance away from Trondheim, as well as having travelled a significant distance during her childhood years. SK196 was chosen because she belonged to a genetic haplogroup suggesting her ancestry was not local to Trondheim or Norway, and this case is also a good example of how genetic and isotopic evidence can work together to create a clearer picture of life history.These three individuals were not chosen at random and can, by no means, be said to represent the whole spectrum of the population in medieval Trondheim; three individuals never can. However, they have been chosen to represent some of the variety within the population while at the same time not being outliers in society. Their place of burial provides a clue as to their position in society. The ecclesiastical parts of the provincial laws , which were in operation at the time these people died, give different regulations about burials. The most important in this context is that the graveyards should be socially stratified, with the upper layers of society being buried close to the church and the people pertaining to the opposite end of the social hierarchy being buried close to the graveyard fence Their ages at death ranges from early twenties for SK152 to early thirties for SK259. This may seem young, but would have been more like the norm than the exception in the Middle-Ages. A recent study from medieval England shows that the great majority of the adult population died before the age of 40 and nearly half before the age of 30 .What about their places of origin and mobility patterns, can that be said to be representative of the population in medieval Trondheim? A recent study of mobility in the population in Trondheim  showed tThe sex of this person was determined morphologically by Trevor Anderson to be female , a concl18O values for the carbonates of the enamel from the first and the third molars are 21.13‰ and 24.72‰ respectively. Hamre and Daux [18Ow corresponding to the M3 tooth was about -9.33‰ (±1‰), which is compatible with Trondheim. Taking into account the possible effect of breast-feeding effect on the M1 tooth, they have calculated the isotopic gradient the individuals crossed between early childhood and teenage. They have shown that this woman was neither born in, nor near, Trondheim where she ended her life, but in an area where the environmental water was 6‰ to 7.3‰ lighter than in Trondheim, that is with δ18Ow of about -15 to -16.5‰. The δ18Ow values of mean precipitation (GNIP database) and surficial waters [18Ow values at this level of depletion are found in northwestern Russia in the regions of Komi, the Nenets Autonomous Okrug, and even further inland in the southern parts of Krasnoyarsk . Lookinbase and ).18Ow values as low as these are only found northwards along the east coast where there were no settlements at the time. The contemporary settlements on Greenland were found on the southern tip and the southwestern coast and neither of these areas are compatible with this woman’s M1 values. It is also difficult to argue for a North American origin even though contact with the continent had been made a couple of centuries earlier [A birthplace in Greenland is, however, unlikely as δ earlier , 65. Thewww.empop.online, v3/R11; [www.empop.online, v3/R11). Hg H4a has also been found in the Neolithic Cardium Pottery culture in Portugal and Spain (http://www.eupedia.com/europe/Haplogroup_H_mtDNA.shtml).The mitochondrial (mt)DNA Control Region (CR) haplotype of this woman was determined as 16232T 16235G 263G 309.1C 315.1C 523DEL 524DEL aligned against the corrected version  of the f v3/R11; ) nor in The skull was assessed morphologically and anthropometrically. The skull suggested a small, gracile female with mild brow ridges, a sloping jaw line, a moderately wide palate, round orbits and an upright profile. The skull was typically female in skeletal characteristics.The determination of eye morphology is related to the position of the inner and outer canthi and the position of the eyeball in the orbit. Previous research , 46 descResearch has shown that the nasal aperture at its widest point will be three-fifths of the overall width of the soft nose , 71 and The morphology of the mouth is an area of the face where there is more reliance on artistic interpretation. Orthodontic and anatomic research shows that the occlusion of the teeth –79, the The ear shape can also be very difficult to determine. The angle of the ear is considered parallel to the jaw line and if the mastoid processes are directed downward, the earlobe will be attached (adherent), whereas if the mastoid processes point forward, the earlobe will be free , but othThe next stage of the facial depiction process is the addition of a skin layer over the muscle structure to fill the face out to the level of the tissue depth pegs. This skin layer follows the shape of the muscles below, so that the main determinant of facial morphology is anatomical structure. For SK152 minimum European female tissue depth measurements were used to reflect a 13th century diet and lifestyle.Finally, the finished head is textured to add skin colour, eye colour, hair colour and style. Here the advice of experts at Bryggens museum in Bergen was considered using typical hairstyles, and the DNA results informed the choice of brown hair and blue eye colour, and the light skin was considered the most likely based on where she was found and her estimated birthplace. This part of the process was carried out in Face Lab using Adobe Photoshop and a 3D stereolithographic copy of the head was also produced for the museum exhibition.The final head shows a delicate female face with small features and ambiguous ancestry.There is no visible evidence of trauma or pathology on this skeleton. The only potential point of interest is that she had lost her left mandibular second premolar and the alveolus was closed and well healed. There are also no Harris lines visible on the radiograph of the left tibia and there is no evidence of hypoplastic enamel, which suggest that this person did not suffer any severe episodes of either disease or starvation during growth.18O and the mtDNA analyses of this individual, it is possible to perform some qualified speculation regarding this woman’s life history. The isotope result from the first molar tells us that she was born quite far away from Trondheim, in northern regions, while the mtDNA analysis suggests that her maternal ancestry may be found somewhere else again. The haplogroup H4a is mainly found in western and central Europe, but is not common in the geographic regions where this woman could have been born. This suggests that this woman’s maternal ancestors were not native to where she was born. With the haplogroup H4a found principally in central and western Europe and the hot spot being found in northern Spain, one may consider a scenario where the maternal lineage of SK152 can be traced back to one of these more southern or central areas of Europe. Regarding her paternal ancestry, there is no genetic data available, but other information may still prove useful. Her cranial morphology shows some traits which are considered Mongoloid-type (see section 5.2.4.) and the facial depiction  which is consistent with late childhood/early teens spent in the area surrounding Trondheim [18Ow corresponding to the M1 tooth, corrected for a possible weaning effect and taking into account a maximum ±1‰ model error, is between about -14.6‰ and -11.4‰ [18O values compatible with an area close to Trondheim, although probably not to Trondheim itself. Areas in Russia, to the east of the Gulf of Bothnia, can also not be ruled out.The δ18Ow range as depleted as that measured for her M1, the only option on the European mainland would be in the Alps at relatively high altitudes, probably more than 750 metres above sea level . Th. Th18Ow www.empop.online, R11; 70) nor in other online resources, suggesting that this haplotype is rare. This CR haplotype belongs to hg W5a2b. This hg is nested in super-hg W5a which is predominantly found in West Eurasian (Caucasian) individuals in Europe and North America . EMPOP lists W5a matches in central Europe (Germany) and eastern Europe (Poland), while W5a2 is, so far, only found in Germany (http://www.eupedia.com/europe/Haplogroup_W_mtDNA.shtml).The mtDNA CR haplotype of this woman was determined as 16177G 16189C 16223T 16292T 16362C 16519C 73G 150T 189G 194T 195C 204C 207A 263G 315.1C 523DEL 524DEL aligned against the rCRS , 68, 69.The skull was assessed morphologically and anthropometrically. The skull suggested a large, robust female with mild brow ridges, large cheek bones, a square jaw line, a wide palate, angular orbits, large mastoid processes, long facial distances and an upright profile. The skull was typically Caucasoid-type ancestry in skeletal characteristics, but was not typically female. Indeed, this skull showed many male characteristics that suggest the woman was a strong and robust individual.th century diet and lifestyle.The orbit morphology suggested horizontal eye fissures, deep-set eyes and central eyelid folds , 46, 50.Finally, the finished head is textured to add skin colour, eye colour, hair colour and style. Here the advice of experts at Bryggens museum in Bergen was considered using typical hairstyles. The DNA did not provide reliable information regarding the appearance of this individual and the choice of a pale, outdoors complexion, mid-brown hair and blue eye colour was based on what seemed most likely considering where she was found and the estimated birthplace. This part of the process was carried out in Face Lab using Adobe Photoshop.The final head shows a robust and masculine face with wide features and a muscular neck.This woman shows signs of porotic hyperostosis and cribra orbitalia. Porotic hyperostosis is identified macroscopically as areas of pitting and porosity on the outer surface of the cranial vault, while cribra orbitalia is identified as similar lesions on the roofs of the eye sockets. Such porosity is evident as a band stretching centrally across the right parietal bone from the lambdoid to the coronal suture . The pitThe presence and aetiology of such lesions have been reported and discussed for over a century e.g. , 84–88) –88 84–88In the case of this woman, the lesions are well healed and she was not suffering from either deficiency at the time of death and had not done so for a number of years. Whether her anaemia stemmed from her mother, her own childhood condition, or both is difficult to say but it seems likely that her problems lasted well into her teens. Despite her likely deficiency, it does not seem she suffered periods of starvation or severe illness during growth as there are no signs of Harris lines on the radiograph of her tibia, nor of hypoplastic enamel on her teeth.18OW value between -14.6 and -11.4 for the first molar would suggest that this woman was born to the north or east of Trondheim, but combined with the mtDNA information, there is another possibility. The hg W5a2b, to which this woman belongs, is interesting in a Norwegian context, primarily for the reason that it is very rare. Hg W has a very low prevalence in modern day Norway (1.8%) and was the only hg present in modern Norway which was absent from the Viking age material in the largest study of Norwegian aDNA to date [http://www.eupedia.com/europe/Haplogroup_W_mtDNA.shtml). Combining this information with the isotope values from her first and third molars, two scenarios seem possible.At first glance, the δFirst scenario is she was born in Norway with parents, or close ancestors, of central European descent. She would have spent her first years of life either on the coast of the county of Nordland or somewhere inland, between there and a region about 200 kilometres east of Trondheim. Her place of origin could have also been in Sweden on the coast of the Gulf of Bothnia.18OW values as low as -11.4 are in the Alps. Her third molar value is 2.12 points different from her birthplace value which means she lived in a different place in her late childhood/early teen years than where she spent her first few years of life. The δ18OW value calculated from her third molar of -10.36‰ is, however, also a little low and does not leave too many options with regard to places she may have lived during her childhood years. It would have been enough to move to an area of lower altitude but still in mountainous regions as a δ18OW value as depleted as -10.36 is not compatible with lowland areas in central Europe. Following this scenario, she would have moved to Trondheim as an adult. It is, of course, impossible to say with any certainty why she moved northwards to Trondheim. Did she move to Trondheim and settle down there or did she come to Trondheim with the intention of going back but happened to die there? Turning to historical sources may, however, shed light on some likely possibilities. There are two factors that might be considered more interesting than others. One is that she had followed the trading routes across Europe. The other major factor to be considered is that Trondheim was the centre of the Catholic church in Norway and a favourite destination for pilgrimage. The shrine of St. Olav was located in Trondheim and received many visitors, possibly in the thousands each year, mostly from the Nordic countries but also from areas further away, like central Europe. As a pilgrim, it is not unlikely that a young woman would visit Trondheim. If her illnesses still troubled her at the time she moved to Trondheim, she might have ventured to the shrine of St. Olav, since its healing powers were renowned. Otherwise, a change in eating habits, as a result of moving to Trondheim, will likely have cured her of her anaemia, as seafood would have formed a significant part of her Norwegian diet.The second scenario would be that she was born in central Europe and, if this was the case, the isotope value from her first molar makes it possible to pinpoint her birthplace with reasonable accuracy. The only places in central Europe where one may find δCulturally she would likely have been able to fit in considering the close connections through trade and religion. Still, she would have had to struggle with similar issues to those one would face today if moving to a different European country: differing day-to-day customs, different food, different climate, finding friends and work as a foreigner, and there would have been a language barrier she would have had to overcome. Bilingualism is likely to have been part of her skill set.The sex of this person was determined by morphological examination to be male , 16 and 18O values of the carbonates of the enamel from the first and third molars of this man are 23.88‰ and 23.97‰ respectively. The δ18Ow values consistent with the isotopic composition of the M1 are in the range of -10‰ to -13.2‰ which suggests that he was not born in Trondheim, but could have lived not very far away. In geographical terms, this means that this person was most likely born in one of the Norwegian counties of North or South Trøndelag, or possibly in southern Nordland. The Swedish county of Jämtland is equally possible. Moving slightly further away, the coastal areas of the Gulf of Bothnia are also a possibility. There is an overlap between the δ18Ow ranges for M1 and M3 (-10.52 ±1‰), so it is likely that he stayed in the same area in which he was born at least until he reached early adulthood.The δwww.empop.online, R11; [The mtDNA CR haplotype of this man was determined as 195C 263G 315.1C 523DEL 524DEL aligned against the rCRS , 68, 69.ne, R11; ) with mawww.yhrd.org) once in a western European individual living in the Bahamas; very likely a descendant of a European immigrant. The reduced haplotype (minHT) leads to 12 matches in Europe confirming the European descent of that haplotype.The paternally inherited Y-Chromosomal haplotype is: DYS456 = 16; DYS389I = 13; DYS390 = 24; DYS389II = 29; DYS458 = 22; DYS19 = 14; DYS385 = 11,14; DYS393 = 13; DYS391 = 11; DYS439 = 12; DYS635 = 23; DYS392 = 13; YGATAH4 = 12; DYS437 = 15; DYS438 = 12; DYS448 = 19. It is found in the largest Y-Chromosomal forensic database  eye fissures, prominent eyeballs and central eyelid folds , 46, 50 Finally, the finished head is textured to add skin colour, eye colour, hair colour and style. Here the advice of the experts at Bryggens museum in Bergen was considered using typical hairstyles. The DNA did not provide reliable information regarding the appearance of this individual and the choice of light skin, dark blonde hair and blue eye colour was based on what seemed most likely considering where he was found and the estimated birthplace. This part of the process was carried out in Face Lab using Adobe Photoshop and a 3D stereolithographic copy of the head was also produced for the museum exhibition. The final head showed a robust male face with large features.This person had undergone a surgical procedure as is evident by the trepanation in the posterior part of the right parietal bone . The treThis was not an everyday event in medieval Trondheim or in Norway, or in Scandinavia for that matter. This is the only known case of successful trepanation in medieval Norway. Holck  presentsTrepanations were mainly used as treatment for head injuries by draining blood from intracranial haematomas, or removing fractured cranial bone fragments or necrotic bone , 97. ThiThe birthplace of this person puts him among the majority of the population in medieval Trondheim as he was born outside the town but probably not too far away . His hg The three life stories outlined above give an insight into the diversity of Norwegian medieval society. The three individuals were all of average social status and, although they were not chosen completely at random, they represent normal members of society and their stories will not have been unique. As shown by Hamre and Daux , the med


Crosstalk between the ERK cascade and other signaling pathways is one of the means by which it acquires its signaling specificity. Here we identified a direct interaction of both MEK1 and MEK2 with AKT. The interaction is mediated by the proline rich domain of MEK1/2 and regulated by phosphorylation of Ser298 in MEK1, or Ser306 in MEK2, which we identified here as a novel regulatory site. We further developed a blocking peptide, which inhibits the interaction between MEK and AKT, and when applied to cells, affects migration and adhesion, but not proliferation. The specific mechanism of action of the MEK-AKT complex involves phosphorylation of the migration-related transcription factor FoxO1. Importantly, prevention of the interaction results in a decreased metastasis formation in a breast cancer mouse model. Thus, the identified interaction both sheds light on how signaling specificity is determined, and represents a possible new therapeutic target for metastatic cancer. The mammalian cell is under constant stimulation from its surroundings and needs to respond accurately and rapidly in order to function properly and survive. Most extracellular ligands stimulate cellular processes via intracellular signal transduction pathways, which are the main routes of communication between the plasma membrane and intracellular compartmentsUpon growth factor stimulation, the ERK1/2 cascade transmits its signals via a sequential phosphorylation and activation of a core three tires of protein kinases, Raf, MEK1/2, and ERK1/2 downstream of Ras578103). The formed phospholipids then recruit the PH domain of AKT to their vicinity, and this anchors the kinase to the plasma membrane. There, the AKT undergoes two phosphorylations, on Thr308 by PDK1 and on Ser473 mainly by mTORC2 that cause full activation of the kinase. The activity of the pathway is negatively regulated by the lipid phosphatase PTEN21The PI3K/AKT pathway is another major intracellular signaling pathway that acts as a critical signaling node in diverse cellular responses20Previous studies have shown the existence of intricate interplay between several components of the ERK1/2 cascade and the PI3K/AKT pathway, including cross-inhibition, cross-activation and pathways convergence3335363942Since both the ERK1/2 and the PI3K/AKT signaling pathways play critical roles in the transmission of cellular signals, components of these pathways are frequently mutated, hyper-activated, or aberrantly expressed in many human cancers47495152545657Here we identified a novel interaction between AKT of the PI3K/AKT pathway and both MEK1 and MEK2 of the ERK cascade. The interaction is mediated by the PRD of MEK1 and MEK2, and is regulated by phosphorylation of Ser298 in MEK1 or Ser306, which we identified as a phosphorylation site in MEK2. Utilizing a peptide that interferes with the interaction we found that the interaction is required for FOXO1 phosphorylation, cellular migration, and cellular adhesion in tissue culture cells, as well as emergence of metastasis in nude mice. However, it did not significantly affect cellular proliferation or tumor growth in mice. Hence, the MEK-AKT interaction extends the signaling repertoire of the pathways, essentially creating a third independent pathway, and suggests a novel target for treating methastasis formation.in vitro binding assay (−/− mouse embrionic fibroblast (MEFs) we found that MEK2 indeed interacts with AKT, and this was slightly increased upon stimulation  experiment, we found to our surprise that MEK1/2 was present in the precipitate. In order to confirm this initial finding, we overexpressed either MEK1-GFP or MEK2-GFP in COS7 cells and found that both MEKs are indeed able to specifically CoIP with the endogenous AKTs . Importang assay . In thisng assay . A recenmulation . We attred cells . Thus, twt MEK1 was increased upon stimulation with EGF, the interaction of S298D mutant was constantly high, and the interaction of S298A was even lower than basal, regardless of stimulation.As the interaction of MEK with AKT was increased upon stimulation, we suspected that stimuli-dependent phosphorylation of one of the known phosphorylation sites might regulate it. To examine this hypothesis we used a time course assay, in which the correlation between the MEK-AKT interaction and the phosphorylation of activatory sites was tested for both kinases . Interes42Finding that MEK2 interacted with AKT similarly to MEK1, we hypothesized that it has a phosphorylation site that can regulate the interaction as well. Such phosphorylation has never been reported, therefore, we undertook to identify and characterize it. Indeed, alignment between the amino acid sequences of MEK1 and MEK2 discovered a Ser306 in MEK2, as a potential corresponding phosphorylation site . This siNext, we undertook to identify the region in MEK1 responsible for the interaction. Since Ser298 was shown to be important for the interaction, we hypothesized that the binding site lies within the PRD. To examine this possibility and identify the exact binding site, we designed four peptides covering distinct parts of the PRD . In ordeupper panels), both in basal and stimulated cells, although the effect of P#3D was smaller than that of the other two. Thus, the WT peptide that demonstrated routinely the most substantial effect was chosen for further characterization. We then undertook to study the specifcity of the peptide. Importantly, none of the peptides significatly affected the phosphorylations of MEK1  or AKT (Thr308/Ser473). In addition, the peptides did not alter the activatory phosphorylations of either ERK1/2 or AKT’s or their downstream target, GSK3 , a transcription factor which is a known substrate of AKT on Ser256 and other sitesnude mice and primary tumors were allowed to develop for approximately 7 days. The mice were then randomly selected for one of three treatment groups: (1) Peptide#3, (2) Scrambled peptide, and (3) Control (PD184352), which was used here to show whether the effectis downstream of ERK activity. The treatments were administrated i.v. three times a week, for 4 weeks. At the end point of the experiment there were no significant differences in the PT size for the three different treatment groups  CoIP of overexpressed MEK isoforms with Abs for endogenous AKTs, (ii) the reciprocal CoIP of overexpressed AKT isoforms with Abs for endogenous MEKs, (iii) CoIP of endogenous proteins, (iv) in vitro binding assay and (v) PLA. These methods clearly showed that MEK can interact with AKT, and since the results were reproduced in several cell lines, it is likely that this interaction can be found in the majority of cells.The ERK cascade and the PI3K/AKT pathway are two major signaling pathways that regulate many different and even opposing cellular processes including proliferation, differentiation and survival, and in rare cases also apoptosis. Crosstalk between the ERK cascade and other signaling pathways is one of the means by which it directs its signaling specificity. There are several known intersections between the ERK cascade and the PI3K/AKT pathway, which control and regulate a broad spectrum of processes. Here we studied a novel physical interaction between MEK1/2 and AKT, and elucidated its physiological role, discovering a new signalling route, different from those of either ERK cascade or PI3K/AKT pathway . This peptide nicely compete with the interaction of MEK1 and AKTs, probably due to its interaction or masking of the binding site in AKT. Therefore, the sequence of this peptide may provide a clue regarding the binding site in AKT. To look into this point, we utilized ANCHORSmap calculations, which is a computational protein-protein docking program, taking into account that AKT2 is the predominant binding isoform of MEK1. Mapping some of the unique residues of AKT2, that are distinct from that of AKT1 and AKT3, that shows them to form an elongated L-shaped cavity on the surface of AKT2 (residues 268–269 and 302). This region as well as additional residues may provide a Low ΔG  anchoring spots for Peptide#3. Importantly, this interaction does not seem to interfer with the catalytic pocket of AKT2, which is consistent with our observation that the activity of AKT is not required or affected either by the binding to MEK1 or to the peptide , basic Fibroblast Growth Factor (bFGF), Polyethylenimine (PEI), Avidin-FITC and 4′6-diamino-2-phenylindole (DAPI) were purchased from Sigma-Aldrich . Protein A/G PLUS-agarose beads were obtained from Santa Cruz Biotechnology, Inc. . Glutathione beads were purchased from GE-healthcare and Proximity ligation assay kit was from Olink Bioscience . Albumin bovine serum (BSA) was purchased from MP biomedical . Si RNAs and Dharmafect were from Thermo Fisher Scientific . NBT/BCIP developing substrates were purchased from Promega . Soybean trypsin inhibitor (SBTI) was purchased from Biological Industries .αGenAKT, αpERK1/2(pTEY-ERK), αGenERK1/2 and αGenMEK1/2 Abs were from Sigma-Aldrich . αMEK1(H8), and αMEK1(C18) Abs were from Santa Cruz Biotechnology . αpT308AKT, αpS473AKT, αpS218/222MEK, αGenMEK2, αpS256FoxO1 and αGenFoxO1 Abs were from Cell Signaling Technology . αpS298MEK1 Ab was from AbCam . αGFP Ab was from Roche Diagnostics GmbH . αpS306MEK2 Phosphosite-specific Abs for the S306-phosphorylated form of MEK2 were prepared by the Antibody Unit of the Weizmann Institute of Science. The rabbit Abs were generated against a sequence corresponding to residues 298–311 of the human MEK2 that contained a phosphorylated Ser residue: C-PRPPGRPV(pS)GHGMD. Rabbit serum Abs were affinity purified against their immunizing peptide as well as against the non-phosphorylated peptide using the SulfoLink kit .Custom peptides overlapping MEK1 sequence were ordered from Peptide 2.0 : peptide #1 (corresponding residues 253–268) PPPDAKELELMFGCQ, peptide #2 (263–288) MFGCQVEGDAAETPP, peptide #3(283–298) AETPPRPRTPGRPLS, peptide #4 (293–308) GRPLSSTGMDSRPPM and a scrambled peptide PLRTPGSPRARPETP. Peptides used in cell assays were adjoined myristic acid (Myr) on their N-terminus.MEK1/2 were cloned in pEGFP-N1 and AKT1/2/3 were cloned in pEGFP-C1 . Point mutations were performed by site-directed mutagenesis using specific primers and confirmed by DNA sequencing. GST was expressed from pGEX41 . MEK1/2 were cloned in pGJ vector  and flanked by SpeI and NotI restriction sites for the recombinant proteins tagged by GST and 8xHis.HeLa and COS-7 cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 2 mM L-glutamine, 1% Pen/Strep and 10% fetal bovine serum (FBS). MDA-MB-231-RFP (clone #3) cells were generously provided by Prof. Avigdor Scherz, the cells were cultured in RPMI 1640 medium with 2 mM L-glutamine, 1% Pen/Strep, 10% FBS, 1% NaPyr and in the presence of 250 μg/ml hygromycin. All cells were maintained at 37 °C in a humidified atmosphere of 95% air and 5% CO2. Cells were transfected with DNA construct using PEI at 30% confluence and 10% FBS.Cells were grown to 70% confluence on cover-slips as previously describedCells were grown to subconfluence and serum-starved for 16 h (0.1% FBS). After treatments, the cells were rinsed twice with ice-cold PBS and once with ice-cold Buffer A, scraped into Buffer H and disrupted by sonication  on ice. The extracts were centrifuged  and the supernatants were either subjected to co-immunoprecipitation or resuspended and boiled for 5 min in sample buffer. The samples were then subjected to 12% SDS-PAGE and Western blotting with the appropriate Abs, which were detected using alkaline phosphatase or ECL according to the manufacturer’s instructions. A representative western blot of at least three independent experiments is shown for all cases.Cell extracts were produced as described above and incubated for 2 hours  with A/G-agarose beads pre-linked with specific Abs . The bound A/G beads were washed three times with ice-cold CoIP washing buffer. The washed beads were then resuspended with 1.5X sample buffer and boiled.Cell extracts were produced as described and incubated for 2 hrs (4 °C) with A/G-agarose beads (Santa Cruz Biotechnology) pre-linked with specific Abs . The bound A/G beads were sequentially washed once with RIPA buffer, then twice with 0.5 M LiCl and twice with Buffer A. The bound A/G beads were then resuspended in Buffer A containing 0.01% BSA and aliquoted. GST tagged proteins were incubated with the beads 2 hrs (4 °C) then washed and resuspended in 1.5 X sample buffer and boiled.Protein–protein interactions were detected with Duolink PLA Kit (Olink Bioscience), as previously reported by our laboratoryGST, GST-MEK1-8xHis and GST-MEK2–8xHis were expressed in E. coli BL21(DE3)pLysS. Bacterial cells were grown at 30 °C to OD600 nm = 0.5, and the expression of recombinant proteins was induced by 0.5 mM IPTG for 4 to 5 hours. Pelleted bacterial cells were lysed, and purification of recombinant proteins was performed using first glutathione affinity chromatography  and then ion metal affinity chromatography with Ni-NTA His-Bind resin  according to the manufacturer’s protocol. Elutions were dialyzed against PBS , and the amount of purified protein was detected by Bradford method.Cells were grown to subconfluence, serum-starved (0.1% FBS for 16 hrs) and then harvested by trypsinization. The trypsin was inactivated by addition of soybean trypsin inhibitor , and cells were collected by centrifugation, resuspended in starvation DMEM, and held in suspension for 2 hrs at 37 °C (0.5 × 106 cells/ml). Cell culture dishes were precoated  with FN (10 μg/ml). Suspended cells were distributed onto the coated dishes  and incubated at 37 °C for various times following plating. The attached cells were rinsed in PBS and then either fixed in 4% paraformaldehyde  or harvested for CoIP assays. Fixed adherent cells were assessed using methylene blue assay, they were washed once in 0.1 M sodium borate buffer (pH 8.5), and thereafter incubated with 1% methylene blue for 10 min. Excess stain was washed out with double distilled water. Stain was extracted with 0.1 M HCl, and OD595 nm was determined in an ELISA reader.Transwell Assay: The migration of HeLa and MDA-MB-231-RFP cells was assayed in 24-well Transwell plates with polycarbonate filters of 8 μm pores . A suspension of cells (5–6 × 104 cells/200 μl) was placed in the upper chambers. The lower chambers were filled with 600 μl of the corresponding medium with or w/o 20 ng/ml bFGF. Cells were allowed to migrate for 16–18 hrs in the presence of different treatments. Thereafter, cells were removed from the upper compartment of the filter with a cotton swab. Cells that reached the lower surface of the filter were fixed with 3% paraformaldehyde, stained with 0.3% crystal violet, and images were then captured using a digital camera coupled with a microscope. Relative migration was quantified following stain extraction with methanol and a 540 nm measurement in an ELISA reader. “Wound Healing” Assay: COS-7, HeLa and MDA-MB-231-RFP cells were grown to 90–95% confluence. Thereafter, a cell scratch spatula was used to create a fixed-width wound in a cell monolayer, followed by incubation with medium containing 1% FBS with or w/o the presence of peptides. Wound closure was monitored after 16–18 hrs.s.c. to fat pad with 1.5 × 106 MDA-MB-231-RFP cells in 100 μl PBS. Tumors were allowed to develop to the size of ~100 mm3 and then animals were randomly allocated to different treatment groups. Peptide#3, its scrambled control (both at 5 mg/kg concentration) and the MEK inhibitor PD184352 (at 2.5 mg/kg) were administered by injection i.v. into the tail vein, three times a week, for four weeks. To assess any signs of systemic toxicity, body weight was monitored three times per week as well.All animal experiments were approved and carried out in “accordance” with the approved guidelines of the Animal Care and Use Committee of the Weizmann Institute of Science . Female CD-1 nude (HsdHli:CD1-Foxn1nu) mice (Harlan), 6 weeks of age, were inoculated t test (two-tailed) to test for differences between the control and experimental results. Values of p < 0.05 were considered statistically significant.Data are expressed as mean ± S.E. Statistical evaluation was carried out using functional analysis and Student’s How to cite this article: Procaccia, S. et al. Direct binding of MEK1 and MEK2 to AKT induces Foxo1 phosphorylation, cellular migration and metastasis. Sci. Rep.7, 43078; doi: 10.1038/srep43078 (2017).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


In these surfaces, we exploit the magnetic volumetric force to exclude the role of solid–liquid interface in ice formation. We show that these inexpensive surfaces are universal and can be applied to all types of solids (no required micro/nano structuring) with no compromise to their unprecedented properties.Anti-icing surfaces have a critical footprint on daily lives of humans ranging from transportation systems and infrastructure to energy systems, but creation of these surfaces for low temperatures remains elusive. Non-wetting surfaces and liquid-infused surfaces have inspired routes for the development of icephobic surfaces. However, high freezing temperature, high ice adhesion strength, and high cost have restricted their practical applications. Here we report new magnetic slippery surfaces outperforming state-of-the-art icephobic surfaces with a ice formation temperature of −34 °C, 2–3 orders of magnitude higher delay time in ice formation, extremely low ice adhesion strength (≈2 Pa) and stability in shear flows up to Reynolds number of 10 Anti-icing surfaces are useful in our daily life, but creation of these surfaces at low temperatures remains challenging due to the onset of heterogeneous nucleation. Irajizad et al. show a surface design using magnetic fluid that lowers the freezing temperature to −34 °C and ice adhesion strength to 2 Pa. Icephobic surfaces has a crucial role in a wide spectrum of systems including transportation124689101112131415161718202123Here we report a new paradigm and the corresponding surface with exceptional icephobicity, high mobility for liquid and ice, self-healing and stability at high Reynolds numbers. In this new approach, magnetic liquid–liquid interfaces are exploited to achieve these unprecedented characteristics. These liquid–liquid interfaces provide a low-energy interface for heterogeneous ice nucleation with Gibbs energy barrier close to the homogenous limit.et al.28Liquid surfaces are intrinsically smooth and defect-free down to the molecular scale. We used magnetic fluids25TN; average ice nucleation delay time, TN is defined as the ice nucleation temperature of a sessile water droplet placed on a surface when the system of droplet, surface and surrounding is cooled with a slow and quasi-equilibrium approach. TN of MAGSS is compared with the other state-of-the-art icephobic surfaces in TN range of −23 to −26 °C, while MAGSS offer a TN value of −34±1 °C  a geometrical factor , in which θIW denotes the contact angle of the ice–water interface, and x is the ratio of radius of heterogeneous nucleation site to critical ice nucleus radius. The route to exceptional icephobicity is to tune function f to approach unity . Since the magnetic liquid–liquid interface is smooth in molecular scale (see Methods section), x value in MAGSS approaches infinity. We plotted f as a function of x for different values of m in x, f function is independent of x. That is, in MAGSS, exceptional icephobicity is a direct consequence of the m value. We have developed an approach to determine the m value in MAGSS surface , negligible friction to water and ice motion, self-healing characteristics and high shear flow stability. These surfaces (MAGSS) provide a defect-free surface for ice nucleation and thereby lower the ice formation to close to homogenous nucleation limit. These surfaces promise a new paradigm for development of icephobic surfaces in aviation technologies, ocean-going vessels, power transmission lines and wind turbines in extreme environments.−3. This ferrofluid was chosen for its high saturation magnetization. We measured the saturation magnetization of this ferrofluid through the Gouy method3(CH2)10COOH). At a wavenumber of 3,000 cm−1, the peak of carboxylic acid group (−COOH) appears. The peak corresponding to the alkenyl group (R-CH=CH2) appears around a wavenumber of 1,100 cm−1. Traces of other fatty acids such as myristic and palmitic acids can also be seen in the FTIR spectrum. The single domain iron-oxide nano-particles in the ferrofluid are coated with surfactants to be suspended in the ferrofluid matrix. The used surfactants are proprietary information of CMS magnetics Inc. and we could not obtain information on the chemical formulas of these surfactants. To determine the dimensions of the iron-oxide nanoparticles, we diluted the ferrofluid with acetone several times. A smooth Si substrate was prepared by plasma cleaning. A droplet of diluted ferrofluid was deposited on the Si substrate and the liquid was allowed to evaporate. A ring trace of the particles was formed on the surface due to coffee-ring effect. The sample was placed in the scanning probe microscope (Bruker Multimedia 8) and the distribution of particle size was measured. We noted that aggregation of particles occurred in the evaporation process. However, the smallest particles were in the range of 10–20 nm as shown in The ferrofluid used for all experiments was an oil-based ferrofluid from CMS magnetics Inc. (Part Number: FERRO-2OZ). The density of ferrofluid was 1,064 kg mEach substrate was cleaned in a plasma cleaner  for 1 min before its use in the experiments. The neodymium magnet was placed underneath the substrate in order to secure the ferrofluid that was to be added on top of the substrate. The ferrofluid was added using a syringe. Adding a specific volume to a known surface area allowed us to control the thickness of the ferrofluid layer. The thickness of the ferrofluid in our experiments was 300 μm. The surface area of the ferrofluid on the substrate is the same as the surface area of the top surface of the magnet.Data supporting the findings of this study are available within the article and its How to cite this article: Irajizad, P. et al. Magnetic slippery extreme icephobic surfaces. Nat. Commun.7, 13395 doi: 10.1038/ncomms13395 (2016).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary Figures 1-21, Supplementary Tables 1-2, Supplementary Notes 1-7 and Supplementary ReferencesFormation of liquid-liquid interface in MAGSS is demonstrated.High mobility of a water droplet on MAGSS is shown.Low-friction surface of MAGSS offers exceptional mobility of liquid droplets.Minimal surface tilt is sufficient for sliding of a water droplet on MAGSS.Exceptional low ice adhesion on MAGSS is demonstrated.Self-healing characteristic of MAGSS under impact of water droplets is shown.High-viscosity MAGSS minimizes the surface disturbance by the droplet impact.Self-healing characteristic of MAGSS under scratching or heating by a sharp object is demonstrated.Long-term stability of MAGSS exposed to airflow is shown. No change in surface characteristics is observed even until Reynolds number of 105.Long-term stability of MAGSS exposed to water flow is shown.


The crystal structure adopts the BaTaS3 structure type and consists of face-sharing [MS6]  octahedra (point-group symmetry -3m.) that are condensed into infinite chains along [001]. Adjacent chains are linked through the barium cations (site symmetry -6m2), which exhibit a coordination number of twelve. The M site is occupied by 2/3 of TaV and 1/3 of CuII, whereby the average M—S distances are slightly longer than those of ordered BaTaS3. The classical charge balance of the title compound can be represented by [Ba2+] [(Ta/Cu)4+] [S2−]3.The mixed-metal title compound, BaCu Here we report on the synthesis and structural characterization of the mixed-metal trisulfide with composition BaCu1/3Ta2/3S3.Barium vanadium trisulfide, BaVS1/3Ta2/3S3 adopts the BaTaS3 structure type in space group P63/mmc. A detailed description of this structure type has been given previously , one mixed-occupied (Cu/Ta) site (2a) and one S site (6h). The structure contains face-sharing octahedral [MS6]  units, which construct infinite chains along [001]  Å, which is slightly longer than that of ordered BaTaS3  and CuII (0.73 Å) using the data provided by Shannon ⋯ distance within a chain is 2.9159 (3) Å, which is much shorter than the interchain ⋯ distance of 6.8437 (18) Å. The Ba—S interactions between adjacent metal sulfide chains are reflected by one shorter [3.422 (6) Å] and one longer distance [3.523 (3) Å], in good agreement with those found in other barium tantalum sulfides 4+] [S2−]3.The classical charge balance of the title compound can be represented by the formula [Ba−1) to 973 K, where it was kept for 2 d. The tube was then cooled to 673 K at a rate of 3 K h−1 and then quenched to room temperature. The crystals are stable in air and alcohol.The title compound was prepared using solid-state reactions between the elements Cu, Ta, S and BaS. Ta powder , Cu powder , S powder , and BaS powder  were mixed in a fused-silica tube in an Ta:Cu:S:BaS molar ratio of 0.67:0.33:2:1. The tube was evacuated to 0.1 Pa, sealed and heated gradually (60 K hScanning electron microscopy (SEM) images of selected crystals were taken on a Hitachi S-4800 microscope equipped with an electron microprobe analyzer for a semiquantitative elemental analysis in the energy dispersive X-ray spectroscopy (EDX) mode. The presence of both copper and tantalum was confirmed Fig. 3.M site resulted in a significant decrease of the reliability factors in comparison with a fully occupied Ta site . No evidence, e.g. in the form of superstructure reflections, was found for an ordering of this site and thus a statistically disordered model was considered. In the final model, atoms of the disordered site were restrained to have the same displacement parameters, with a fixed Cu:Ta ratio of 1/3:2/3 required for charge neutrality and in good agreement with the EDX measurement. The remaining maximum and minimum electron densities are located 1.06 Å from the 1 site and 1.96 Å from the S1, respectively.Crystal data, data collection and structure refinement details are summarized in Table 110.1107/S2056989017005266/wm5362sup1.cifCrystal structure: contains datablock(s) global, I. DOI: 10.1107/S2056989017005266/wm5362Isup3.hklStructure factors: contains datablock(s) I. DOI: 1542709CCDC reference:  crystallographic information; 3D view; checkCIF reportAdditional supporting information:


Arctic sea ice provides microhabitats for biota that inhabit the liquid‐filled network of brine channels and the ice–water interface. We used meta‐analysis of 23 published and unpublished datasets comprising 721 ice cores to synthesize the variability in composition and abundance of sea ice meiofauna at spatial scales ranging from within a single ice core to pan‐Arctic and seasonal scales. Two‐thirds of meiofauna individuals occurred in the bottom 10 cm of the ice. Locally, replicate cores taken within meters of each other were broadly similar in meiofauna composition and abundance, while those a few km apart varied more; 75% of variation was explained by station. At the regional scale (Bering Sea first‐year ice), meiofauna abundance varied over two orders of magnitude. At the pan‐Arctic scale, the same phyla were found across the region, with taxa that have resting stages or tolerance to extreme conditions  dominating abundances. Meroplankton, however, was restricted to nearshore locations and landfast sea ice. Light availability, ice thickness, and distance from land were significant predictor variables for community composition on different scales. On a seasonal scale, abundances varied broadly for all taxa and in relation to the annual ice algal bloom cycle in both landfast and pack ice. Documentation of ice biota composition, abundance, and natural variability is critical for evaluating responses to decline in Arctic sea ice. Consistent methodology and protocols must be established for comparability of meiofauna monitoring across the Arctic. We recommend to (1) increase taxonomic resolution of sea ice meiofauna, (2) focus sampling on times of peak abundance when seasonal sampling is impossible, (3) include the bottom 30 cm of ice cores rather than only bottom 10 cm, (4) preserve specimens for molecular analysis to improve taxonomic resolution, and (5) formulate a trait‐based framework that relates to ecosystem functioning. The botx¯), relative standard error (RSE=100%×SE/x¯), and taxonomic group contribution were calculated for a 1° latitude × 2° longitude grid.At the regional scale of tens to hundreds of kilometers, data from 59 sites within the central and northern Bering Sea Figure , sampledThe entire synthesized dataset was used to examine meiofauna composition and abundance patterns on the pan‐Arctic scale Figure . The ArcSeparating seasonal fluctuations (and researcher bias) from geographic differences in the entire compiled dataset is difficult. We, therefore, present two seasonal datasets, each collected and analyzed by a consistent researcher team and collected within a small area to remove at least part of the geographic variation: The first study was a multiyear study conducted in Barrow Alaska [Figure 2.2www.marinespecies.org): Chromista including unicellular organisms such as Ciliophora, Foraminifera, and Radiozoa; flatworms including Acoela and PlatyhelminthesMost studies reported sea ice meiofauna using coarse taxonomic groupings as few taxonomic experts have studied these groups in sea ice, and several taxa do not preserve well with conventional preservatives. Consequently, meiofauna were grouped as follows, using the current taxonomic classification in the World Register of Marine Species (2.32.3.12) using functions described in Appendix We used three different metrics to describe our datasets: (1) frequency of occurrence (FO), which presents the proportion of ice cores containing one or more specimens of a given taxon. (2) Abundance metrics used in the published sources were converted to individuals (ind.) per square meter of sea ice  was run for regional‐scale Bering Sea and pan‐Arctic meiofauna aggregate percentage data  of all meiofauna were found in the bottom 10 cm , but there was a trend for higher aggregate percentages of flatworms, meroplankton, and nauplii in the bottom 0‐ to 10‐cm sections and a lower contribution of those groups in midsections.In the 64 entire cores analyzed, two‐thirds . Specifically, stations at ≤10 m bottom depth had one to two orders of magnitude higher total abundances than those at >10 m depth. Stations ≤10 m also had higher contributions of meroplanktonic stages of benthic taxa, in particular a single species of polychaete, Scolelepis squamata, than those >10 m. Stations >10 m were similar to each other in total abundance, but varied in composition. Nauplii were essentially absent at stations ≤10 m, but were prominent at stations >10 m and in some replicates in Elson Lagoon. Copepods (excluding nauplii) consisted almost at equal parts of harpacticoids (55%) and calanoids (45%). Replicates taken at a single station within about 1 m2 within 4 days in April 2007 were in five of seven cases broadly similar in composition and abundance. In one of the seven cases . The dominant taxon in the Bering Sea was Rotifera, which in the majority of grid cells contributed >50% of all individuals. In some grid cells near land , however, other taxa contributed equal or higher proportions including nematodes, meroplankton, flatworms, and—in a single grid cell—Copepoda  and exceeded those of many shelf and basin locations (pack ice locations) by an order of magnitude , similarly to bottom depth and distance from land  as well as ice thickness and snow depth . Interestingly, chlorophyll a concentration did not significantly correlate with any of the environmental variables. On a taxonomically resolved level, only meroplankton demonstrated both biologically and statistically meaningful relationships with environmental variables, in that meroplankton showed a negative relationship with distance from land  and bottom depth (.28). The vector fitting again indicated that meroplankton tended to occur in higher abundances close to land, whereas copepod abundance increased with distance from land and depth  thought to feed not only on ice algae but also on bacteria and dissolved organic matter or other nematodes  occur across the Arctic ice cover, although relative proportions varied widely. It is unclear if the similarity in taxa present is also true at the species level given the general lack of identification to species or even genus, although recent mapping of the sparse species‐level records available suggests that broad species distribution ranges across the Arctic ice cover may indeed be common .The data are available in the Norwegian Polar Institute's database (None declared.BB, HH, and MV wrote the manuscript; BB and HH designed the “experiment”; MV, BB, HH, IAM, RG, IK, and JS collected the data; MV, BB, and RG analyzed the data; BB, HH, IK, RG, MV, JS, and IAM revised the manuscript. Click here for additional data file.