Neither dust nor black carbon causing apparent albedo decline in Greenland\u27s dry snow zone: Implications for MODIS C5 surface reflectance

Remote sensing observations suggest Greenland ice sheet (GrIS) albedo has declined since 2001, even in the dry snow zone. We seek to explain the apparent dry snow albedo decline. We analyze samples representing 2012–2014 snowfall across NW Greenland for black carbon and dust light-absorbing impurities (LAI) and model their impacts on snow albedo. Albedo reductions due to LAI are small, averaging 0.003, with episodic enhancements resulting in reductions of 0.01–0.02. No significant increase in black carbon or dust concentrations relative to recent decades is found. Enhanced deposition of LAI is not, therefore, causing significant dry snow albedo reduction or driving melt events. Analysis of Collection 5 Moderate Resolution Imaging Spectroradiometer (MODIS) surface reflectance data indicates that the decline and spectral shift in dry snow albedo contains important contributions from uncorrected Terra sensor degradation. Though discrepancies are mostly below the stated accuracy of MODIS products, they will require revisiting some prior conclusions with C6 data

Bone morphogenetic protein 7 sensitizes O6-methylguanine methyltransferase expressing-glioblastoma stem cells to clinically relevant dose of temozolomide.

BackgroundTemozolomide (TMZ) is an oral DNA-alkylating agent used for treating patients with glioblastoma. However, therapeutic benefits of TMZ can be compromised by the expression of O6-methylguanine methyltransferase (MGMT) in tumor tissue. Here we used MGMT-expressing glioblastoma stem cells (GSC) lines as a model for investigating the molecular mechanism underlying TMZ resistance, while aiming to explore a new treatment strategy designed to possibly overcome resistance to the clinically relevant dose of TMZ (35 μM).MethodsMGMT-expressing GSC cultures are resistant to TMZ, and IC50 (half maximal inhibitory concentration) is estimated at around 500 μM. Clonogenic GSC surviving 500 μM TMZ (GSC-500 μM TMZ), were isolated. Molecular signatures were identified via comparative analysis of expression microarray against parental GSC (GSC-parental). The recombinant protein of top downregulated signature was used as a single agent or in combination with TMZ, for evaluating therapeutic effects of treatment of GSC.ResultsThe molecular signatures characterized an activation of protective stress responses in GSC-500 μM TMZ, mainly including biotransformation/detoxification of xenobiotics, blocked endoplasmic reticulum stress-mediated apoptosis, epithelial-to-mesenchymal transition (EMT), and inhibited growth/differentiation. Bone morphogenetic protein 7 (BMP7) was identified as the top down-regulated gene in GSC-500 μM TMZ. Although augmenting BMP7 signaling in GSC by exogenous BMP7 treatment did not effectively stop GSC growth, it markedly sensitized both GSC-500 μM TMZ and GSC-parental to 35 μM TMZ treatment, leading to loss of self-renewal and migration capacity. BMP7 treatment induced senescence of GSC cultures and suppressed mRNA expression of CD133, MGMT, and ATP-binding cassette drug efflux transporters (ABCB1, ABCG2), as well as reconfigured transcriptional profiles in GSC by downregulating genes associated with EMT/migration/invasion, stemness, inflammation/immune response, and cell proliferation/tumorigenesis. BMP7 treatment significantly prolonged survival time of animals intracranially inoculated with GSC when compared to those untreated or treated with TMZ alone (p = 0.0017), whereas combination of two agents further extended animal survival compared to BMP7 alone (p = 0.0489).ConclusionsThese data support the view that reduced endogenous BMP7 expression/signaling in GSC may contribute to maintained stemness, EMT, and chemoresistant phenotype, suggesting that BMP7 treatment may provide a novel strategy in combination with TMZ for an effective treatment of glioblastoma exhibiting unmethylated MGMT

Deep Experimental Profiling of microRNA Diversity, Deployment, and Evolution Across the \u3ci\u3eDrosophila\u3c/i\u3e Genus

To assess miRNA evolution across the Drosophila genus, we analyzed several billion small RNA reads across 12 fruit fly species. These data permit comprehensive curation of species- and clade-specific variation in miRNA identity, abundance, and processing. Among well-conserved miRNAs, we observed unexpected cases of clade-specific variation in 5′ end precision, occasional antisense loci, and putatively noncanonical loci. We also used strict criteria to identify a large set (649) of novel, evolutionarily restricted miRNAs. Within the bulk collection of species-restricted miRNAs, two notable subpopulations are splicing-derived mirtrons and testes-restricted, recently evolved, clustered (TRC) canonical miRNAs. We quantified miRNA birth and death using our annotation and a phylogenetic model for estimating rates of miRNA turnover. We observed striking differences in birth and death rates across miRNA classes defined by biogenesis pathway, genomic clustering, and tissue restriction, and even identified flux heterogeneity among Drosophila clades. In particular, distinct molecular rationales underlie the distinct evolutionary behavior of different miRNA classes. Mirtrons are associated with high rates of 3′ untemplated addition, a mechanism that impedes their biogenesis, whereas TRC miRNAs appear to evolve under positive selection. Altogether, these data reveal miRNA diversity among Drosophila species and principles underlying their emergence and evolution

Deep Experimental Profiling of MicroRNA Diversity, Deployment, and Evolution Across the \u3ci\u3eDrosphila\u3c/i\u3e Genus

To assess miRNA evolution across the Drosophila genus, we analyzed several billion small RNA reads across 12 fruit fly species. These data permit comprehensive curation of species- and clade-specific variation in miRNA identity, abundance, and processing. Among well-conserved miRNAs, we observed unexpected cases of clade-specific variation in 5′ end precision, occasional antisense loci, and putatively noncanonical loci. We also used strict criteria to identify a large set (649) of novel, evolutionarily restricted miRNAs. Within the bulk collection of species-restricted miRNAs, two notable subpopulations are splicing-derived mirtrons and testes-restricted, recently evolved, clustered (TRC) canonical miRNAs. We quantified miRNA birth and death using our annotation and a phylogenetic model for estimating rates of miRNA turnover. We observed striking differences in birth and death rates across miRNA classes defined by biogenesis pathway, genomic clustering, and tissue restriction, and even identified flux heterogeneity among Drosophila clades. In particular, distinct molecular rationales underlie the distinct evolutionary behavior of different miRNA classes. Mirtrons are associated with high rates of 3′ untemplated addition, a mechanism that impedes their biogenesis, whereas TRC miRNAs appear to evolve under positive selection. Altogether, these data reveal miRNA diversity among Drosophila species and principles underlying their emergence and evolution

IVF versus IUI with ovarian stimulation for unexplained infertility : a collaborative individual participant data meta-analysis

Funding Information: WL is supported by a NHMRC Investigator grant (GNT2016729). RW is supported by an NHMRC Investigator grant (GNT20009767). BWM is supported by a NHMRC Investigator grant (GNT1176437) and he reports consultancy for ObsEva and Merck and travel support from Merck.Peer reviewe

Tuberculosis treatment monitoring tests during routine practice : study design guidance

Funding: CMD reports project-specific funding from WHO; grants for various projects on TB diagnostics development and evaluation support from FIND, Geneva; grants for Rapid Research in Diagnostics Development (R2D2) for TB network from National Institutes of Health (NIH) US; grants for various projects on TB diagnostics development and evaluation from German Center for Infectious Disease Research (DZIF). EL-HM reports support for this project from the New Diagnostics Working GroupdBiomarkers Taskforce. Funding for the study was provided by the New Diagnostics Working Group-Biomarkers Taskforce. The New Diagnostics Working Group was supported by funding received from the Stop TB Partnership and USAID.Scope The current tools for tuberculosis (TB) treatment monitoring, smear microscopy and culture, cannot accurately predict poor treatment outcomes. Research into new TB treatment monitoring tools (TMT) is growing, but data are unreliable. In this document, we aim to provide guidance for studies investigating and evaluating TB TMT for use during routine clinical care. Here, a TB TMT would guide treatment during the course of therapy, rather test for cure at the regimen’s end. This document does not cover the use of TB TMTs as surrogate endpoints in the clinical trial context. Methods Guidelines were initially informed by experiences during a systematic review of TB TMTs. Subsequently, a small content expert group was consulted for feedback on initial recommendations. After revision, feedback from substantive experts across sectors was sought. Questions addressed by the guideline and Recommendations The proposed considerations and recommendations for studies evaluating TB TMTs for use during treatment in routine clinical care fall into eight domains. We provide specific recommendations regarding study design and recruitment; outcome definitions; reference standards; participant follow-up; clinical setting; study population; treatment regimen reporting; and index tests and data presentation. Overall, TB TMTs should be evaluated in a manner similar to diagnostic tests, but TB TMT accuracy must be assessed at multiple timepoints throughout the treatment course, and TB TMTs should be evaluated in study populations who have already received a diagnosis of TB. Study design and outcome definitions must be aligned with the developmental phase of the TB TMT under evaluation. There is no gold standard for TB treatment response, so different reference standards and comparator tests have been proposed, the selection of which will vary depending on the developmental phase of the TMT under assessment. The use of comparator tests can assist in generating evidence. Clarity is required when reporting of timepoints, TMT read-outs, and analysis results. Implementing these recommendations will lead to higher quality TB TMT studies which will allow data to be meaningfully compared, thereby facilitating the development of novel tools to guide individual TB therapy and improve treatment outcomes.Peer reviewe

SIV-specific CD8+ T cells are clonotypically distinct across lymphoid and mucosal tissues

CD8+ T cell responses are necessary for immune control of simian immunodeficiency virus (SIV). However, the key parameters that dictate antiviral potency remain elusive, conceivably because most studies to date have been restricted to analyses of circulating CD8+ T cells. We conducted a detailed clonotypic, functional, and phenotypic survey of SIV-specific CD8+ T cells across multiple anatomical sites in chronically infected rhesus macaques with high (>10,000 copies/mL plasma) or low burdens of viral RNA (<10,000 copies/mL plasma). No significant differences in response magnitude were identified across anatomical compartments. Rhesus macaques with low viral loads (VLs) harbored higher frequencies of polyfunctional CXCR5+ SIV-specific CD8+ T cells in various lymphoid tissues and higher proportions of unique Gag-specific CD8+ T cell clonotypes in the mesenteric lymph nodes relative to rhesus macaques with high VLs. In addition, public Gag-specific CD8+ T cell clonotypes were more commonly shared across distinct anatomical sites than the corresponding private clonotypes, which tended to form tissue-specific repertoires, especially in the peripheral blood and the gastrointestinal tract. Collectively, these data suggest that functionality and tissue localization are important determinants of CD8+ T cell–mediated efficacy against SIV

Insights into technical challenges in the field of microplastic pollution through the lens of early career researchers (ECRs) and a proposed pathway forward

Early career researchers (ECR) face a series of challenges related to the inherent difficulties of starting their careers. Microplastic (MP) research is a topical field attracting high numbers of ECRs with diverse backgrounds and expertise from a wealth of disciplines including environmental science, biology, chemistry and ecotoxicology. In this perspective the challenges that could hinder scientific, professional, or personal development are explored, as identified by an international network of ECRs, all employed in MP research, that was formed following a bilateral workshop for scientists based in the UK and China. Discussions amongst the network were grouped into four overarching themes of technical challenges: in the field, in the laboratory, in the post data collection phase, and miscellaneous. The three key areas of representativeness, access to appropriate resources, training, and clean labs, and the use of databases and comparability, as well as the overarching constraint of available time were identified as the source of the majority of challenges. A set of recommendations for pathways forward are proposed based on the principles of research openness, access to information and training, and widening collaborations. ECRs have great capacity to promote research excellence in the field of MPs and elsewhere, when provided with appropriate opportunities and suitable support

Perivascular epitheloid cell tumour (PEComa) of the retroperitoneum – a rare tumor with uncertain malignant behaviour: a case report

<p>Abstract</p> <p>Introduction</p> <p>Perivascular epitheloid cell tumours are rare mesenchymal neoplasms characterized by a proliferation of perivascular cells with an epitheloid phenotype and expression of myomelanocytic markers.</p> <p>Case presentation</p> <p>Here we present the case of a cystic perivascular epitheloid cell tumour of the retroperitoneum associated with multifocal lung lesions. A 27-year-old woman underwent laparotomy to remove a 10 × 6 × 4 cm sized retroperitoneal mass. The resected specimen was subjected to frozen and permanent histological sections with conventional and immunohistochemical stains, including antibodies against HMB45. The tumour displayed the typical morphological and immunohistochemical features of a perivascular epitheloid cell tumour. Focal necrosis and a proliferative index of 10% suggested a malignant potential. Moreover, postoperative computed tomography scans demonstrated multiple lung lesions, which were radiologically interpreted as being most likely compatible with lymphangioleiomyomatosis.</p> <p>Conclusion</p> <p>Since lymphangioleiomyomatosis, an otherwise benign condition, belongs to the family of perivascular epitheloid cell tumours, it cannot be excluded that the lung lesions in this case in fact represent metastases from the retroperitoneal perivascular epitheloid cell tumour rather than independent neoplasms. More experience with this new and unusual tumour entity is clearly needed in order to define reliable criteria for benign or malignant behaviour.</p

Unusual magnetic field responsive circularly polarized luminescence probes with highly emissive chiral europium(III) complexes

Chirality is ubiquitous within biological systems where many of the roles and functions are still undetermined. Given this, there is a clear need to design and develop sensitive chiral optical probes that can function within a biological setting. Here we report the design and synthesis of magnetically responsive Circularly Polarized Luminescence (CPL) complexes displaying exceptional photophysical properties (quantum yield up to 31 % and |glum| up to 0.240) by introducing chiral substituents onto the macrocyclic scaffolds. Magnetic CPL responses are observed in these chiral EuIII complexes, promoting an exciting development to the field of magneto-optics. The |glum| of the 5D0 → 7F1 transition increases by 20 % from 0.222 (0 T) to 0.266 (1.4 T) displaying a linear relationship between the Δglum and the magnetic field strength. These EuIII complexes with magnetic CPL responses, provides potential development to be used in CPL imaging applications due to improved sensitivity and resolution