Correlation between synthesis of ?2-macroglobulin in hepatocytes and changes in serum cytokine levels in rats after infl ammatory stimulation

The time course of ?2-macroglobulin (?2M) synthesis in rat liver was investigated using immunohistochemistry. Furthermore, correlations between synthesis of ?2M in hepatocytes and interleukin (IL)-6 and cytokine-induced neutrophil chemoattractant-1 (CINC-1), which are considered to contribute to the production of ?2M, were evaluated. The presence of ?2M in the liver was investigated by immunohistochemistry, and serum levels of ?2M, IL-6 and CINC-1 were measured by enzyme-linked immunosorbent assay. ?2M was not detected in the liver before injection of turpentine oil. ?2M was detected throughout the liver at 12 hours after injection of turpentine oil, when high serum levels of IL-6 and CINC-1 were observed. ?2M was distributed mainly around the central vein of the liver at 36 hours. Only small amounts of ?2M were detected in the liver at 48 hours, when peak serum levels of ?2M were observed. Synthesis of ?2M in hepatocytes peaked long before peak ?2M serum levels were seen. In conclusion, ?2M was considered to be synthesized in response to stimulation by IL-6 and CINC-1

Coupled-wave model for square-lattice photonic-crystal lasers with TE polarization -- a general approach

A general coupled-wave model is presented for square-lattice photonic crystal (PC) lasers with transverse-electric polarization. This model incorporates the high-order coupling effects that are important for two-dimensional PC laser cavities and gives a general and rigorous coupled-wave formulation for the full three-dimensional structures of typical laser devices. Numerical examples based on our model are presented for PC structures with different air-hole shapes. The accuracy of the results obtained is verified using three-dimensional finite-difference time-domain simulations

Classifying caesarean section to understand rising rates among Palestinian refugees: results from 290,047 electronic medical records across five settings

BACKGROUND: Rising caesarean-section rates worldwide are driven by non-medically indicated caesarean-sections. A systematic review concluded that the ten-group classification system (Robson) is the most appropriate for assessing drivers of caesarean deliveries. Evidence on the drivers of caesarean-section rates from conflict-affected settings is scarce. This study examines caesareans-section rates among Palestinian refugees by seven-group classification, compares to WHO guidelines, and to rates in the host settings, and estimates the costs of high rates. METHODS: Electronic medical records of 290,047 Palestinian refugee women using UNRWA's (United Nations Relief and Works Agency for Palestine Refugees in the Near East) antenatal service from 2017-2020 in five settings (Jordan, Lebanon, Syria, West Bank, Gaza) were used. We modified Robson criteria to compare rates within each group with WHO guidelines. The host setting data were extracted from publicly available reports. Data on costs came from UNRWA's accounts. FINDINGS: Palestinian refugees in Gaza had the lowest caesarean-section rates (22%), followed by those residing in Jordan (28%), West Bank (30%), Lebanon (50%) and Syria (64%). The seven groups caesarean section classification showed women with previous caesarean-sections contributed the most to overall rates. Caesarean-section rates were substantially higher than the WHO guidelines, and excess caesarean-sections (2017-2020) were modelled to cost up to 6.8 million USD. We documented a steady increase in caesarean-section rates in all five settings for refugee and host communities; refugee rates paralleled or were below those in their host country. INTERPRETATION: Caesarean-section rates exceed recommended guidance within most groups. The high rates in the nulliparous groups will drive future increases as they become multiparous women with a previous caesarean-section and in turn, face high caesarean rates. Our analysis helps suggest targeted and tailored strategies to reduce caesarean-section rates in priority groups (among low-risk women) organized by those aimed at national governments, and UNRWA, and those aimed at health-care providers

Classifying caesarean section to understand rising rates among Palestinian refugees: results from 290,047 electronic medical records across five settings

Background: Rising caesarean-section rates worldwide are driven by non-medically indicated caesarean-sections. A systematic review concluded that the ten-group classifcation system (Robson) is the most appropriate for assessing drivers of caesarean deliveries. Evidence on the drivers of caesarean-section rates from confictafected settings is scarce. This study examines caesareans-section rates among Palestinian refugees by seven-group classifcation, compares to WHO guidelines, and to rates in the host settings, and estimates the costs of high rates.Methods: Electronic medical records of 290,047 Palestinian refugee women using UNRWA’s (United Nations Relief and Works Agency for Palestine Refugees in the Near East) antenatal service from 2017–2020 in fve settings (Jordan, Lebanon, Syria, West Bank, Gaza) were used. We modifed Robson criteria to compare rates within each group with WHO guidelines. The host setting data were extracted from publicly available reports. Data on costs came from UNRWA’s accounts.Findings: Palestinian refugees in Gaza had the lowest caesarean-section rates (22%), followed by those residing in Jordan (28%), West Bank (30%), Lebanon (50%) and Syria (64%). The seven groups caesarean section classifcation showed women with previous caesarean-sections contributed the most to overall rates. Caesarean-section rates were substantially higher than the WHO guidelines, and excess caesarean-sections (2017–2020) were modelled to cost up to 6.8 million USD. We documented a steady increase in caesarean-section rates in all fve settings for refugee and host communities; refugee rates paralleled or were below those in their host country.Interpretation: Caesarean-section rates exceed recommended guidance within most groups. The high rates in the nulliparous groups will drive future increases as they become multiparous women with a previous caesareansection and in turn, face high caesarean rates. Our analysis helps suggest targeted and tailored strategies to reduce caesarean-section rates in priority groups (among low-risk women) organized by those aimed at national governments, and UNRWA, and those aimed at health-care providers

Successful Long-Term Preservation of Rat Sperm by Freeze-Drying

Background: Freeze-drying sperm has been developed as a new preservation method where liquid nitrogen is no longer necessary. An advantage of freeze-drying sperm is that it can be stored at 4uC and transported at room temperature. Although the successful freeze-drying of sperm has been reported in a number of animals, the possibility of long-term preservation using this method has not yet been studied. Methodology/Principal Findings: Offspring were obtained from oocytes fertilized with rat epididymal sperm freeze-dried using a solution containing 10 mM Tris and 1 mM EDTA adjusted to pH 8.0. Tolerance of testicular sperm to freeze-drying was increased by pre-treatment with diamide. Offspring with normal fertility were obtained from oocytes fertilized with freeze-dried epididymal sperm stored at 4uC for 5 years. Conclusions and Significance: Sperm with –SS – cross-linking in the thiol-disulfide of their protamine were highly tolerant to freeze-drying, and the fertility of freeze-dried sperm was maintained for 5 years without deterioration. This is the first report to demonstrate the successful freeze-drying of sperm using a new and simple method for long-term preservation

Identification and Specification of the Mouse Skeletal Stem Cell

SummaryHow are skeletal tissues derived from skeletal stem cells? Here, we map bone, cartilage, and stromal development from a population of highly pure, postnatal skeletal stem cells (mouse skeletal stem cells, mSSCs) to their downstream progenitors of bone, cartilage, and stromal tissue. We then investigated the transcriptome of the stem/progenitor cells for unique gene-expression patterns that would indicate potential regulators of mSSC lineage commitment. We demonstrate that mSSC niche factors can be potent inducers of osteogenesis, and several specific combinations of recombinant mSSC niche factors can activate mSSC genetic programs in situ, even in nonskeletal tissues, resulting in de novo formation of cartilage or bone and bone marrow stroma. Inducing mSSC formation with soluble factors and subsequently regulating the mSSC niche to specify its differentiation toward bone, cartilage, or stromal cells could represent a paradigm shift in the therapeutic regeneration of skeletal tissues

Characterization of collective ground states in single-layer NbSe2

Layered transition metal dichalcogenides (TMDs) are ideal systems for exploring the effects of dimensionality on correlated electronic phases such as charge density wave (CDW) order and superconductivity. In bulk NbSe2 a CDW sets in at TCDW = 33 K and superconductivity sets in at Tc = 7.2 K. Below Tc these electronic states coexist but their microscopic formation mechanisms remain controversial. Here we present an electronic characterization study of a single 2D layer of NbSe2 by means of low temperature scanning tunneling microscopy/spectroscopy (STM/STS), angle-resolved photoemission spectroscopy (ARPES), and electrical transport measurements. We demonstrate that 3x3 CDW order in NbSe2 remains intact in 2D. Superconductivity also still remains in the 2D limit, but its onset temperature is depressed to 1.9 K. Our STS measurements at 5 K reveal a CDW gap of {\Delta} = 4 meV at the Fermi energy, which is accessible via STS due to the removal of bands crossing the Fermi level for a single layer. Our observations are consistent with the simplified (compared to bulk) electronic structure of single-layer NbSe2, thus providing new insight into CDW formation and superconductivity in this model strongly-correlated system.Comment: Nature Physics (2015), DOI:10.1038/nphys352

Antibody-Directed Lentiviral Gene Transduction for Live-Cell Monitoring and Selection of Human iPS and hES Cells

The identification of stem cells within a mixed population of cells is a major hurdle for stem cell biology–in particular, in the identification of induced pluripotent stem (iPS) cells during the reprogramming process. Based on the selective expression of stem cell surface markers, a method to specifically infect stem cells through antibody-conjugated lentiviral particles has been developed that can deliver both visual markers for live-cell imaging as well as selectable markers to enrich for iPS cells. Antibodies recognizing SSEA4 and CD24 mediated the selective infection of the iPS cells over the parental human fibroblasts, allowing for rapid expansion of these cells by puromycin selection. Adaptation of the vector allows for the selective marking of human embryonic stem (hES) cells for their removal from a population of differentiated cells. This method has the benefit that it not only identifies stem cells, but that specific genes, including positive and negative selection markers, regulatory genes or miRNA can be delivered to the targeted stem cells. The ability to specifically target gene delivery to human pluripotent stem cells has broad applications in tissue engineering and stem cell therapies

Ionizing radiation modulates human macrophages towards a pro-inflammatory phenotype preserving their pro-invasive and pro-angiogenic capacities

In order to improve the efficacy of conventional radiotherapy, attention has been paid to immune cells, which not only modulate cancer cell response to therapy but are also highly recruited to tumours after irradiation. Particularly, the effect of ionizing radiation on macrophages, using therapeutically relevant doses, is not well understood. To evaluate how radiotherapy affects macrophage behaviour and macrophage-mediated cancer cell activity, human monocyte derived-macrophages were subjected, for a week, to cumulative ionizing radiation doses, as used during cancer treatment (2Gy/fraction/day). Irradiated macrophages remained viable and metabolically active, despite DNA damage. NF-kappaB transcription activation and increased Bcl-xL expression evidenced the promotion of pro-survival activity. A significant increase of pro-inflammatory macrophage markers CD80, CD86 and HLA-DR, but not CCR7, TNF and IL1B was observed after 10Gy cumulative doses, while anti-inflammatory markers CD163, MRC1, VCAN and IL-10 expression decreased, suggesting the modulation towards a more proinflammatory phenotype. Moreover, ionizing radiation induced macrophage morphological alterations and increased their phagocytic rate, without affecting matrix metalloproteases (MMP)2 and MMP9 activity. Importantly, irradiated macrophages promoted cancer cell-invasion and cancer cell-induced angiogenesis. Our work highlights macrophage ability to sustain cancer cell activities as a major concern that needs to be addressed to improve radiotherapy efficacy

Dasatinib impairs long-term expansion of leukemic progenitors in a subset of acute myeloid leukemia cases

A number of signaling pathways might be frequently disrupted in acute myeloid leukemia (AML). We questioned whether the dual SRC/ABL kinase inhibitor dasatinib can affect AML cells and whether differences can be observed with normal CD34+ cells. First, we demonstrated that normal cord blood (CB) CD34+ cells were unaffected by dasatinib at a low concentration (0.5 nM) in the long-term culture on MS5 stromal cells. No changes were observed in proliferation, differentiation, and colony formation. In a subset of AML cases (3/15), a distinct reduction in cell proliferation was observed, ranging from 48% to 91% inhibition at 0.5 nM of dasatinib, in particular, those characterized by BCR–ABL or KIT mutations. Moreover, the inhibitory effects of dasatinib were cytokine specific. Stem cell factor-mediated proliferation was significantly impaired, associated with a reduced phosphorylation of ERK1/2 and STAT5, whereas no effect was observed on interleukin-3 and thrombopoietin-mediated signaling despite SRC activation. In conclusion, this study demonstrates that dasatinib is a potential inhibitor in a subgroup of AML, especially those that express BCR–ABL or KIT mutations