Extreme enriched and heterogeneous ⁸⁷Sr/⁸⁶Sr ratios recorded in magmatic plagioclase from the Samoan hotspot

We report the major-element, trace-element, and 87Sr/86Sr compositions of six plagioclase crystals from two Samoan lavas with extreme EM2 isotopic compositions (ALIA-115-18 with whole-rock 87Sr/86Sr of 0.718592, and ALIA-115-21 with whole-rock 87Sr/86Sr of 0.720469). We employed laser-ablation split-stream mass spectrometry (LASS) to simultaneously measure 87Sr/86Sr ratios, major-element concentrations, and trace-element concentrations in the same plagioclase crystal volume. We find that two plagioclase crystals have extreme 87Sr/86Sr heterogeneity in excess of 5000 ppm (where ppm of 87Sr/Sr variability86=106⋅[Sr/8687Srmax−87Sr/86Srmin]/87Sr/86Sravg). In two of the plagioclase crystals, we identify the highest 87Sr/86Sr ratios (0.7224) ever measured in any fresh, mantle-derived ocean island basalt (OIB) or OIB-hosted mineral phase.We find that in 87Sr/86Sr-versus-Sr concentration space, the six plagioclase crystals overlap in a “common component” region with higher 87Sr/86Sr than has been previously identified in whole-rock Samoan lavas or mineral separates. We use the occurrence of olivine mineral inclusions (Fo=74.5±0.8, 2 SD) in the high-87Sr/86Sr zone of one plagioclase crystal to infer the bulk composition (Mg#=46.8±0.8, 2 SD) of the extreme EM2 magma from which the olivine and high-87Sr/86Sr plagioclase crystallized. We argue that a relatively evolved EM2 endmember magma mixed with at least one lower-87Sr/86Sr melt to generate the observed intra-crystal plagioclase isotopic heterogeneity.By inferring that subducted terrigenous sediment gives rise to EM2 signatures in Samoan lavas, we estimate that the quantity of sediment necessary to generate the most-elevated 87Sr/86Sr ratios observed in the Samoan plagioclase is ∼7% of the mantle source. We also estimate that sediment subduction into the mantle over geologic time has generated a sediment domain that constitutes 0.02% of the mass of the mantle, a much lower proportion than required in the EM2 mantle source. Even if subducted sediment is concentrated in large low-shear-velocity provinces (LLSVPs) at the base of the mantle (which constitute up to 7.7% of the mantle's mass), then only 0.25% of the LLSVPs are composed of sediment. This requires that the distribution of subducted sediment in the mantle is heterogeneous, and the high relative abundance of sediment in the Samoan EM2 mantle is an anomalous relic of ancient subduction that has survived convective attenuation

Dynamics of DNA replication loops reveal temporal control of lagging-strand synthesis

In all organisms, the protein machinery responsible for the replication of DNA, the replisome, is faced with a directionality problem. The antiparallel nature of duplex DNA permits the leading-strand polymerase to advance in a continuous fashion, but forces the lagging-strand polymerase to synthesize in the opposite direction. By extending RNA primers, the lagging-strand polymerase restarts at short intervals and produces Okazaki fragments. At least in prokaryotic systems, this directionality problem is solved by the formation of a loop in the lagging strand of the replication fork to reorient the lagging-strand DNA polymerase so that it advances in parallel with the leading-strand polymerase. The replication loop grows and shrinks during each cycle of Okazaki fragment synthesis. Here we use single-molecule techniques to visualize, in real time, the formation and release of replication loops by individual replisomes of bacteriophage T7 supporting coordinated DNA replication. Analysis of the distributions of loop sizes and lag times between loops reveals that initiation of primer synthesis and the completion of an Okazaki fragment each serve as a trigger for loop release. The presence of two triggers may represent a fail-safe mechanism ensuring the timely reset of the replisome after the synthesis of every Okazaki fragment.

A review of a strategic roadmapping exercise to advance clinical translation of photoacoustic imaging: From current barriers to future adoption

Photoacoustic imaging (PAI), also referred to as optoacoustic imaging, has shown promise in early-stage clinical trials in a range of applications from inflammatory diseases to cancer. While the first PAI systems have recently received regulatory approvals, successful adoption of PAI technology into healthcare systems for clinical decision making must still overcome a range of barriers, from education and training to data acquisition and interpretation. The International Photoacoustic Standardisation Consortium (IPASC) undertook an community exercise in 2022 to identify and understand these barriers, then develop a roadmap of strategic plans to address them. Here, we outline the nature and scope of the barriers that were identified, along with short-, medium- and long-term community efforts required to overcome them, both within and beyond the IPASC group

Trajectory of vitamin D status during pregnancy in relation to neonatal birth size and fetal survival: a prospective cohort study

Background: We investigated the associations between vitamin D status in early and late pregnancy with neonatal small for gestational age (SGA), low birth weight (LBW) and preterm delivery. Furthermore, associations between vitamin D status and pregnancy loss were studied. Methods: Serum 25-hydroxyvitamin D (25OHD) was sampled in gestational week ≤ 16 (trimester 1 (T1), N = 2046) and > 31 (trimester 3 (T3), N = 1816) and analysed using liquid chromatography tandem mass spectrometry. Pregnant women were recruited at antenatal clinics in south-west Sweden at latitude 57–58°N. Gestational and neonatal data were retrieved from medical records. Multiple gestations and terminated pregnancies were excluded from the analyses. SGA was defined as weight and/or length at birth < 2 SD of the population mean and LBW as < 2500 g. Preterm delivery was defined as delivery < 37 + 0 gestational weeks and pregnancy loss as spontaneous abortion or intrauterine fetal death. Associations between neonatal outcomes and 25OHD at T1, T3 and change in 25OHD (T3-T1) were studied using logistic regression. Results: T1 25OHD was negatively associated with pregnancy loss and 1 nmol/L increase in 25OHD was associated with 1% lower odds of pregnancy loss (OR 0.99, p = 0.046). T3 25OHD ≥ 100 nmol/L (equal to 40 ng/ml) was associated with lower odds of SGA (OR 0.3, p = 0.031) and LBW (OR 0.2, p = 0.046), compared to vitamin D deficiency (25OHD < 30 nmol/L, or 12 ng/ml). Women with a ≥ 30 nmol/L increment in 25OHD from T1 to T3 had the lowest odds of SGA, LBW and preterm delivery. Conclusions: Vitamin D deficiency in late pregnancy was associated with higher odds of SGA and LBW. Lower 25OHD in early pregnancy was only associated with pregnancy loss. Vitamin D status trajectory from early to late pregnancy was inversely associated with SGA, LBW and preterm delivery with the lowest odds among women with the highest increment in 25OHD. Thus, both higher vitamin D status in late pregnancy and gestational vitamin D status trajectory can be suspected to play a role in healthy pregnancy

Leprosy among Patient Contacts: A Multilevel Study of Risk Factors

Leprosy is an infectious disease that can lead to physical disabilities, social stigma, and great hardship. Transmitted from person to person, it is still endemic in developing countries, like Brazil and India. Effective treatment has been available since 1960, but early diagnosis of the disease remains the most effective way to stop the transmission chain and avoid late diagnoses and subsequent disabilities. Knowledge of the risk factors for leprosy can facilitate early detection; therefore, our study aimed to investigate the factors presented by leprosy patients and their contacts, who are considered at highest risk of contracting the disease. We studied 6,158 contacts of 1,201 patients under surveillance from 1987 to 2007 in a Public Health Care Center in the City of Rio de Janeiro, Brazil. We evaluated the ways patient and contact demographics and epidemiological characteristics were associated with the detection of leprosy. Statistical analyses took into account both individual and group characteristics and their interrelationships. The main characteristics facilitating the contraction of leprosy among contacts were shown to be consanguinity and household association. Conversely, the bacillary load index of leprosy patients was the principle factor leading to disease among their contacts

Dehydration of subducting slow-spread oceanic lithosphere in the Lesser Antilles

Subducting slabs carry water into the mantle and are a major gateway in the global geochemical water cycle. Fluid transport and release can be constrained with seismological data. Here we use joint active-source/local-earthquake seismic tomography to derive unprecedented constraints on multi-stage fluid release from subducting slow-spread oceanic lithosphere. We image the low P-wave velocity crustal layer on the slab top and show that it disappears beneath 60–100 km depth, marking the depth of dehydration metamorphism and eclogitization. Clustering of seismicity at 120–160 km depth suggests that the slab’s mantle dehydrates beneath the volcanic arc, and may be the main source of fluids triggering arc magma generation. Lateral variations in seismic properties on the slab surface suggest that serpentinized peridotite exhumed in tectonized slow-spread crust near fracture zones may increase water transport to sub-arc depths. This results in heterogeneous water release and directly impacts earthquakes generation and mantle wedge dynamics

Natural and anthropogenic changes to mangrove distributions in the Pioneer River Estuary (QLD, Australia)

We analyzed a time series of aerial photographs and Landsat satellite imagery of the Pioneer River Estuary (near Mackay, Queensland, Australia) to document both natural and anthropogenic changes in the area of mangroves available to filter river runoff between 1948 and 2002. Over 54 years, there was a net loss of 137 ha (22%) of tidal mangroves during four successive periods that were characterized by different driving mechanisms: (1) little net change (1948– 1962); (2) net gain from rapid mangrove expansion (1962–1972); (3) net loss from clearing and tidal isolation (1972–1991); and (4) net loss from a severe species-specific dieback affecting over 50% of remaining mangrove cover (1991–2002). Manual digitization of aerial photographs was accurate for mapping changes in the boundaries of mangrove distributions, but this technique underestimated the total loss due to dieback. Regions of mangrove dieback were identified and mapped more accurately and efficiently after applying the Normalized Difference Vegetation Index (NDVI) to Landsat Thematic Mapper satellite imagery, and then monitoring changes to the index over time. These remote sensing techniques to map and monitor mangrove changes are important for identifying habitat degradation, both spatially and temporally, in order to prioritize restoration for management of estuarine and adjacent marine ecosystems

TNFα Cooperates with IFN-γ to Repress Bcl-xL Expression to Sensitize Metastatic Colon Carcinoma Cells to TRAIL-mediated Apoptosis

BACKGROUND: TNF-related apoptosis-inducing ligand (TRAIL) is an immune effector molecule that functions as a selective anti-tumor agent. However, tumor cells, especially metastatic tumor cells often exhibit a TRAIL-resistant phenotype, which is currently a major impediment in TRAIL therapy. The aim of this study is to investigate the synergistic effect of TNFα and IFN-γ in sensitizing metastatic colon carcinoma cells to TRAIL-mediated apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: The efficacy and underlying molecular mechanism of cooperation between TNFα and IFN-γ in sensitizing metastatic colon carcinoma cells to TRAIL-mediated apoptosis were examined. The functional significance of TNFα- and IFN-γ-producing T lymphocyte immunotherapy in combination with TRAIL therapy in suppression of colon carcinoma metastasis was determined in an experimental metastasis mouse model. We observed that TNFα or IFN-γ alone exhibits minimal sensitization effects, but effectively sensitized metastatic colon carcinoma cells to TRAIL-induced apoptosis when used in combination. TNFα and IFN-γ cooperate to repress Bcl-xL expression, whereas TNFα represses Survivin expression in the metastatic colon carcinoma cells. Silencing Bcl-xL expression significantly increased the metastatic colon carcinoma cell sensitivity to TRAIL-induced apoptosis. Conversely, overexpression of Bcl-xL significantly decreased the tumor cell sensitivity to TRAIL-induced apoptosis. Furthermore, TNFα and IFN-γ also synergistically enhanced TRAIL-induced caspase-8 activation. TNFα and IFN-γ was up-regulated in activated primary and tumor-specific T cells. TRAIL was expressed in tumor-infiltrating immune cells in vivo, and in tumor-specific cytotoxic T lymphocytes (CTL) ex vivo. Consequently, TRAIL therapy in combination with TNFα/IFN-γ-producing CTL adoptive transfer immunotherapy effectively suppressed colon carcinoma metastasis in vivo. CONCLUSIONS/SIGNIFICANCE: TNFα and IFN-γ cooperate to overcome TRAIL resistance at least partially through enhancing caspase 8 activation and repressing Bcl-xL expression. Combined CTL immunotherapy and TRAIL therapy hold great promise for further development for the treatment of metastatic colorectal cancer