Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcriptomic Profiling Revealed Plexin A2 Downregulation With Migration and Invasion Alteration in Dacarbazine-Treated Primary Melanoma Cells

Melanoma is highly heterogeneous type of malignant neoplasm that is responsible for the majority of deaths among other types of skin cancer. In the present study, we screened a list of differentially expressed genes in two primary, drug-naïve melanoma cell lines derived from patients with melanoma following treatment of the cells with the chemotherapeutic agent dacarbazine. The aim was to determine the transcriptomic profiles and associated alterations in the cell phenotype. We found the vascular endothelial growth factor A/vascular endothelial growth factor receptor 2, phosphoinositide 3-kinase/protein kinase B and focal adhesion signaling pathways to be top altered after dacarbazine treatment. In addition, we observed the expression levels of genes associated with tumor dissemination, integrin β8 and matrix metalloproteinase-1, to be diminished in both cell lines studied, the results of which were confirmed by reverse transcription-quantitative polymerase chain reaction. By contrast, plexin A2 expression was found to be upregulated in K2303 cells, where reduced migration and invasion were also observed, following dacarbazine treatment. Plexin A2 downregulation was associated with the promotion of migrative and invasive capacities in B0404 melanoma cells. Since plexin A2 is semaphorin co-receptor that is involved in focal adhesion and cell migration regulation, the present study suggested that plexin A2 may be implicated in the dacarbazine-mediated phenotypic shift of melanoma cells. We propose that the signature of cancer cell invasiveness can be revealed by using a combination of transcriptomic and functional approaches, which should be applied in the development of personalized therapeutic strategies for each patient with melanoma.
The Impact of Long-Run Macroeconomic Experiences on Personality

Using two datasets containing demographically representative samples of the Dutch population, I study how lifetime experiences of aggregate labor market conditions affect personality. Three sets of findings are reported. First, experienced aggregate unemployment is negatively correlated with the levels of all Big Five personality traits, except for conscientiousness (no significant correlation). Second, in panel data models with individual fixed effects I find that changes in experienced aggregate unemployment cause changes in emotional stability and agreeableness for men, and conscientiousness for women. The correlation is positive, and effects are economically large. Thirdly, I report suggestive evidence that the main driver is experienced aggregate unemployment, instead of other macroeconomic variables as experienced GDP, stock market returns or inflation. Taken together, these findings suggest that changes in Big Five personality traits are systematically related to experienced aggregate labor market conditions.
Involvement of the Mitogen-activated Protein Kinase c-Jun NH2-terminal Kinase 1 in Thrombus Formation*

The involvement of the mitogen-activated protein kinase c-Jun NH2-terminal kinase-1 (JNK1) has never been investigated in hemostasis and thrombosis. Using two JNK inhibitors (SP600125 and 6o), we have demonstrated that JNK1 is involved in collagen-induced platelet aggregation dependent on ADP. In these conditions, JNK1 activation requires the coordinated signaling pathways of collagen receptors (α2β1 and glycoprotein (GP)VI) and ADP. In contrast, JNK1 is not required for platelet adhesion on a collagen matrix in static or blood flow conditions (300–1500 s–1) involving collagen receptors (α2β1 and GPVI). Importantly, at 1500 s–1, JNK1 acts on thrombus formation on a collagen matrix dependent on GPIb-von Willebrand factor (vWF) interaction but not ADP receptor activation. This is confirmed by the involvement of JNK1 in shear-induced platelet aggregation at 4000 s–1. We also provide evidence during rolling and adhesion of platelets to vWF that platelet GPIb-vWF interaction triggers αIIbβ3 activation in a JNK1-dependent manner. This was confirmed with a Glanzmann thrombastenic patient lacking αIIbβ3. Finally, in vivo, JNK1 is involved in arterial but not in venular thrombosis in mice. Overall, our in vitro studies define a new role of JNK1 in thrombus formation in flowing blood that is relevant to thrombus development in vivo.
Glutamate and Kynurenate in the Rat Central Nervous System Following Treatments with Tail Ischaemia or Diclofenac

Kynurenate is an endogenous antagonist at the allosteric glycine site on the N‐methyl‐D‐aspartate (NMDA) receptor, and may have a role in ameliorating nociceptive processes through modulation of NMDA receptor function. While antinociceptive effects of non‐steroidal anti‐inflammatory drugs (NSAIDs) are mediated peripherally and possibly centrally through inhibition of prostaglandin synthesis, there is also evidence for centrally mediated prostaglandin‐independent antinociceptive effects that may result from increased central nervous system (CNS) concentrations of kynurenate. We have investigated the effects of the NSAID diclofenac, (40 mg kg−1, s.c.; administered to rats 1 h before killing) or the exposure of rats to noxious stimulation (tail ischaemia for 20 min before killing), on the concentrations of glutamate and kynurenate in discrete CNS regions.
Socially Complex Breeding Interactions in Humpback Whales Are Mediated Using a Complex Acoustic Repertoire

Intraspecific conflict can be costly; therefore, many species engage in ritualized contests composed of several stages. Each stage is typically characterized by different levels of aggression, arousal, and physical conflict. During these different levels of “intensity,” animals benefit from communicating potential information related to features such as resource holding potential, relative fighting ability, level of aggression, intent (i.e., fight or flight), and whether or not the competitor currently holds the resource (e.g., a receptive female). This information may be conveyed using both visual displays and a complex acoustic repertoire containing fixed (e.g., age, sex, and body size) and flexible information (e.g., motivation or arousal). Calls that contain fixed information are generally considered “discrete” or stereotyped, while calls that convey flexible information are more “graded,” existing along an acoustic continuum. The use of displays and calls, and the potential information they convey, is likely dependent on factors like intensity level. The breeding system of humpback whales (Megaptera novaeangliae) involves intense male competition for access to a relatively limited number of breeding females (the resource). Here, we investigated the behavior and acoustic repertoire of competitive groups of humpback whales to determine if an increase in intensity level of the group was correlated with an increase in the complexity of the vocal repertoire. We categorized the behavior of humpback whales in competitive groups into three mutually exclusive stages from low to high intensity. While discrete calls were infrequent compared to graded calls overall, their use was highest in “low” and “moderate” intensity groups, which may indicate that this stage of contest is important for assessing the relative resource holding potential of competitors. In contrast, visual displays, call rates, and the use of graded call types, were highest during “high intensity” competitive groups. This suggests that flexible information may be more important in “high intensity” levels as males continue to assess the motivation and intent of competitors while actively engaged in costly conflict. We have shown that the relatively complex social call repertoire and visual displays of humpback whales in competitive groups likely functions to mediate frequently changing within-group relationships.
Religiosity/Spirituality and Substance Use in Adolescence as Related to Positive Development: A Literature Review

AbstractPositive youth development interventions are strategies to address adolescent health risk behaviors and are recommended in Healthy People 2020. Although the incorporation of spirituality into these programs has been recommended, much of the empirical literature actually addresses religiosity rather than spirituality. The purpose of our review of 36 studies published between 2007 and 2013 was to (1) examine the relationship of religiosity and/or spirituality to substance use and abuse in adolescence, (2) discuss the measurement and meaning of the concept of spirituality in contrast to religiosity in adolescence, and (3) discuss the implications of these empirical studies for the concept of positive youth development. Findings from this literature review supported earlier findings of an inverse relationship between religiosity and substance use, a lack of or inconsistent definition of spirituality and religiosity as well as limited measures to address these constructs. Recommendations from this review include dedicated work by interdisciplinary teams to address consistency in definitions and creation of consistent tools that include consideration of the stages of development included in the adolescent years. From a research and clinical perspective, an interprofessional approach to clarify the concepts of spirituality and spiritual development would not only benefit research but could inform the substance abuse prevention field. This work is essential to insure that evidence-based strategies, which include religiosity and spirituality, are developed with the goal of protecting youth and supporting positive development of adolescents.
Perceptions of Options Available for Victims of Physical Intimate Partner Violence in Northern India

We used qualitative methodologies to understand perceptions regarding options available for victims of physical intimate partner violence (IPV) in northern India. We interviewed male and female community members along with IPV experts. Interviews were transcribed, coded, and analyzed using grounded theory. Participants emphasized that a victim of physical IPV should bear the violence, modify her husbands’ behaviors, or seek help from her natal family. Accessing external resources such as the police or nongovernmental organizations was viewed as both socially inappropriate and infeasible. These results have widespread implications and lay the foundation for the development of IPV prevention initiatives in India.
Protection of nude rats against Toxoplasma infection by excreted-secreted antigen-specific helper T cells

In the present work we demonstrate the implication of excreted-secreted antigens in eliciting the protective cell-mediated immunity developed by rats toward Toxoplasma gondii. We first showed that 10(4) specific T cells from T. gondii-infected rats conferred to nude rats the ability to resist an infection by the highly virulent RH strain of T. gondii. In a second series of experiments, the role of excreted-secreted antigens in this protection was demonstrated. After the adoptive transfer to nude rats of various doses (10(3), 10(4), 10(5)) of excreted-secreted antigen-specific helper T cells (propagated in vitro during one month), significant protection toward T. gondii was induced. Moreover, these cells were responsible for a specific antibody response in nude rats, which are normally unable to develop any specific humoral response. The specificity of these antibodies was directed toward different molecules with molecular masses of 104, 97, 57, 39, 30, 21, and 18 kilodaltons; some of these have been previously characterized as major excreted-secreted antigens.
Transcriptomic Response to Perkinsus marinus in Two Crassostrea Oysters Reveals Evolutionary Dynamics of Host-Parasite Interactions

Infectious disease outbreaks are causing widespread declines of marine invertebrates including corals, sea stars, shrimps, and molluscs. Dermo is a lethal infectious disease of the eastern oyster Crassostrea virginica caused by the protist Perkinsus marinus. The Pacific oyster Crassostrea gigas is resistant to Dermo due to differences in the host-parasite interaction that is not well understood. We compared transcriptomic responses to P. marinus challenge in the two oysters at early and late infection stages. Dynamic and orchestrated regulation of large sets of innate immune response genes were observed in both species with remarkably similar patterns for most orthologs, although responses in C. virginica were stronger, suggesting strong or over-reacting immune response could be a cause of host mortality. Between the two species, several key immune response gene families differed in their expansion, sequence variation and/or transcriptional response to P. marinus, reflecting evolutionary divergence in host-parasite interaction. Of note, significant upregulation of inhibitors of apoptosis (IAPs) was observed in resistant C. gigas but not in susceptible C. virginica, suggesting upregulation of IAPs is an active defense mechanism, not a passive response orchestrated by P. marinus. Compared with C. gigas, C. virginica exhibited greater expansion of toll-like receptors (TLRs) and positive selection in P. marinus responsive TLRs. The C1q domain containing proteins (C1qDCs) with the galactose-binding lectin domain that is involved in P. marinus recognition, were only present and significantly upregulated in C. virginica. These results point to previously undescribed differences in host defense genes between the two oyster species that may account for the difference in susceptibility, providing an expanded portrait of the evolutionary dynamics of host-parasite interaction in lophotrochozoans that lack adaptive immunity. Our findings suggest that C. virginica and P. marinus have a history of coevolution and the recent outbreaks may be due to increased virulence of the parasite.
Heterologous protein secretion in Lactococcus lactis: a novel antigen delivery system.

Lactic acid bacteria (LAB) are Gram-positive bacteria and are generally regarded as safe (GRAS) organisms. Therefore, LAB could be used for heterologous protein secretion and they are good potential candidates as antigen delivery vehicles. To develop such live vaccines, a better control of protein secretion is required. We developed an efficient secretion system in the model LAB, Lactococcus lactis. Staphylococcal nuclease (Nuc) was used as the reporter protein. We first observed that the quantity of secreted Nuc correlated with the copy number of the cloning vector. The nuc gene was cloned on a high-copy number cloning vector and no perturbation of the metabolism of the secreting strain was observed. Replacement of nuc native promoter by a strong lactococcal one led to a significant increase of nuc expression. Secretion efficiency (SE) of Nuc in L. lactis was low, i.e., only 60% of the synthesized Nuc was secreted. Insertion of a synthetic propeptide between the signal peptide and the mature moiety of Nuc increased the SE of Nuc. On the basis of these results, we developed a secretion system and we applied it to the construction of an L. lactis strain which secretes a bovine coronavirus (BCV) epitopeprotein fusion (BCV-Nuc). BCV-Nuc was recognized by both anti-BCV and anti-Nuc antibodies. Secretion of this antigenic fusion is the first step towards the development of a novel antigen delivery system based on LAB-secreting strains.
Engineering, Characterization, and Biological Evaluation of an Antibody Targeting the HGF Receptor

The Hepatocyte growth factor (HGF) and its receptor (MET) promote several physiological activities such as tissue regeneration and protection from cell injury of epithelial, endothelial, neuronal and muscle cells. The therapeutic potential of MET activation has been scrutinized in the treatment of acute tissue injury, chronic inflammation, such as renal fibrosis and multiple sclerosis (MS), cardiovascular and neurodegenerative diseases. On the other hand, the HGF-MET signaling pathway may be caught by cancer cells and turned to work for invasion, metastasis, and drug resistance in the tumor microenvironment. Here, we engineered a recombinant antibody (RDO24) and two derived fragments, binding the extracellular domain (ECD) of the MET protein. The antibody binds with high affinity (8 nM) to MET ECD and does not cross-react with the closely related receptors RON nor with Semaphorin 4D. Deletion mapping studies and computational modeling show that RDO24 binds to the structure bent on the Plexin-Semaphorin-Integrin (PSI) domain, implicating the PSI domain in its binding to MET. The intact RDO24 antibody and the bivalent Fab2, but not the monovalent Fab induce MET auto-phosphorylation, mimicking the mechanism of action of HGF that activates the receptor by dimerization. Accordingly, the bivalent recombinant molecules induce HGF biological responses, such as cell migration and wound healing, behaving as MET agonists of therapeutic interest in regenerative medicine. In vivo administration of RDO24 in the murine model of MS, represented by experimental autoimmune encephalomyelitis (EAE), delays the EAE onset, mitigates the early clinical symptoms, and reduces inflammatory infiltrates. Altogether, these results suggest that engineered RDO24 antibody may be beneficial in multiple sclerosis and possibly other types of inflammatory disorders.
The Cold Avoidance of Typhoons in Their North Turning Over the South China Sea

Based on the typhoon best tracks of the China Meteorological Administration (CMA), ERA5 reanalysis data of ECMWF at 0.25 degrees horizontal resolution, and NOAA optimal interpolated sea surface temperature (OISST V2) data, the dynamical compositing analysis is used to study the north turning at nearly 90 degrees of 4 westward typhoons over the South China Sea (SCS). The composite analysis results show that: (1) As the typhoon goes westward into the SCS, the upper-level westerly trough moves eastward to the vicinity of 110°E in the mainland of China, and the western North Pacific subtropical high (SH) retreats eastward at the same time, which weakens the steering flow of typhoon and slowes down its movement. (2) The cold air guided by the westerly trough invades southwardly into the western part of SCS from the mainland leading to a descending and divergent airflow in the lower-to-middle atmospheric layers and enhancing the eastward pressure gradient force (PGF) in the west quadrant of the typhoon, which blocks and repesl the typhoon from moving any further westward. (3) Due to the cold air intrusion, the vertical atmospheric stratification in the west quadrant of the typhoon becomes static and stable, which may suppress the convection, impeding a typhoon’s westward motion. (4) With the cold air involving to the south of the typhoon, the direction of the PGF on the typhoon switches from eastward to northward, and the SH falling southward enhances the southwesterly airflow on the south of the typhoon at the same time. The remarkable increase of the northward steering airflows of the typhoon results in an abrupt northward turn. (5) In addition, the sea surface temperature (SST) and the ocean heat content (OHC) on the western part of the SCS is also reduced, attributed to the cold air cooling, and the typhoon is likely to avoid the cold ocean and approach a relatively warmer region. This study suggests that cold avoidance during the westward movement of typhoons is worthy of consideration in the operational forecast of typhoon tracks.
MICROX-an all-silicon technology for monolithic microwave integrated circuits

An improved silicon-on-insulator (SOI) approach offers devices and circuits operating to 10 GHz by providing formerly unattainable capabilities in bulk silicon: reduced junction-to-substrate capacitances in FETs and bipolar transistors, inherent electrical isolation between devices, and low-loss microstrip lines. The concept, called MICROX (patent pending), is based on the SIMOX process, but uses very-high-resistivity (typically>10000 Omega -cm) silicon substrates, MICROX NMOS transistors of effective gate length 0.25 mu m give a maximum frequency of operation, f/sub max/, of 32 GHz and f/sub T/ of 23.6 GHz in large-periphery (4 mu m*50 mu m) devices with no correction for the parasitic effects of the pads. The measured minimum noise figure is 1.5 dB at 2 GHz with associated gain of 17.5 dB, an improvement over previously reported values for silicon FETs. <<ETX>>
Lower Bifidobacteria counts in both duodenal mucosa-associated and fecal microbiota in irritable bowel syndrome patients.

AIM To determine the composition of both fecal and duodenal mucosa-associated microbiota in irritable bowel syndrome (IBS) patients and healthy subjects using molecular-based techniques. METHODS Fecal and duodenal mucosa brush samples were obtained from 41 IBS patients and 26 healthy subjects. Fecal samples were analyzed for the composition of the total microbiota using fluorescent in situ hybridization (FISH) and both fecal and duodenal brush samples were analyzed for the composition of bifidobacteria using real-time polymerase chain reaction. RESULTS The FISH analysis of fecal samples revealed a 2-fold decrease in the level of bifidobacteria (4.2 +/- 1.3 vs 8.3 +/- 1.9, P < 0.01) in IBS patients compared to healthy subjects, whereas no major differences in other bacterial groups were observed. At the species level, Bifidobacterium catenulatum levels were significantly lower (6 +/- 0.6 vs 19 +/- 2.5, P < 0.001) in the IBS patients in both fecal and duodenal brush samples than in healthy subjects. CONCLUSION Decreased bifidobacteria levels in both fecal and duodenal brush samples of IBS patients compared to healthy subjects indicate a role for microbiotic composition in IBS pathophysiology.
An Integrated Moral Obligation Model for Landowner Conservation Norms

ABSTRACT This study applies an integrated moral obligation model to examine the role of environmental and cultural values, and beliefs in the activation of landowner conservation norms. Data for this study were collected through a self-administered survey of riparian landowners in two Minnesota watersheds: Sand Creek and Vermillion River watersheds. Study findings suggest that collectivistic and biospheric–altruistic values form the bases for the activation of personal norms. Further, beliefs about local responsibility and ability to act influence personal norms to protect water resources. Findings suggest that landowners’ personal norms of water conservation are more likely to be activated by conservation strategies that appeal to biospheric–altruistic and collectivistic values, emphasize adverse consequences of water pollution, highlight water resource protection as a local responsibility, and provide the resources needed to protect water resources.