Sulfidation enhances stability and mobility of carboxymethyl cellulose stabilized nanoscale zero-valent iron in saturated porous media

Sulfidation can enhance the reactivity and longevity of nanoscale zero-valent iron (nZVI), but little is known about its effect on the fate and transport of nZVI in saturated porous media. This work compared the stability and mobility of carboxymethyl cellulose (CMC) stabilized nZVI (CMC-nZVI) and sulfidated nZVI (CMC-S-nZVI) particles in saturated porous media. After sulfidation, the hydrodynamic size of CMC-S-nZVI was 100–150 nm larger than CMC-nZVI due to enhanced adsorption of CMC onto the S-nZVI surface, which was facilitated by the bidentate bridging interaction between CMC and the FeSx phase on S-nZVI. Of note is that they had a similar core size and zeta potential. In comparison to CMC-nZVI, CMC-S-nZVI exhibited less physical settling (0–5% vs. 5–73%) and chemical dissolution (2–10% vs. 3–27%) within 55 min under the same ionic conditions (Na+, K+ < 200 mM; Al3+ < 0.75 mM). Column breakthrough experiments showed that both CMC-S-nZVI and CMC-nZVI had relatively high mobility in saturated porous media. However, CMC-S-nZVI exhibited greater breakthrough (C/C0 = 0.57–1.0) and corresponding greater mass recovery rates than the corresponding CMC-nZVI (C/C0 = 0.44–1.0) under most of the experimental conditions (e.g., different ion type and concentration, flow rate, and input concentration). The fitted colloid filtration theory model was in good agreement with experiments. This work suggests that in addition to the significant reactivity and longevity improvements demonstrated in other studies, CMC-S-nZVI is also more mobile than CMC-nZVI suggesting that CMC-S-nZVI has many of the characteristics favorable for field application

Reversible Block of Mouse Neural Stem Cell Differentiation in the Absence of Dicer and MicroRNAs

BACKGROUND: To investigate the functions of Dicer and microRNAs in neural stem (NS) cell self-renewal and neurogenesis, we established neural stem cell lines from the embryonic mouse Dicer-null cerebral cortex, producing neural stem cell lines that lacked all microRNAs. PRINCIPAL FINDINGS: Dicer-null NS cells underwent normal self-renewal and could be maintained in vitro indefinitely, but had subtly altered cell cycle kinetics and abnormal heterochromatin organisation. In the absence of all microRNAs, Dicer-null NS cells were incapable of generating either glial or neuronal progeny and exhibited a marked dependency on exogenous EGF for survival. Dicer-null NS cells assumed complex differences in mRNA and protein expression under self-renewing conditions, upregulating transcripts indicative of self-renewing NS cells and expressing genes characteristic of differentiating neurons and glia. Underlining the growth-factor dependency of Dicer-null NS cells, many regulators of apoptosis were enriched in expression in these cells. Dicer-null NS cells initiate some of the same gene expression changes as wild-type cells under astrocyte differentiating conditions, but also show aberrant expression of large sets of genes and ultimately fail to complete the differentiation programme. Acute replacement of Dicer restored their ability to differentiate to both neurons and glia. CONCLUSIONS: The block in differentiation due to loss of Dicer and microRNAs is reversible and the significantly altered phenotype of Dicer-null NS cells does not constitute a permanent transformation. We conclude that Dicer and microRNAs function in this system to maintain the neural stem cell phenotype and to facilitate the completion of differentiation

The RNA m6A Reader YTHDF2 Is Essential for the Post-transcriptional Regulation of the Maternal Transcriptome and Oocyte Competence.

YTHDF2 binds and destabilizes N6-methyladenosine (m6A)-modified mRNA. The extent to which this branch of m6A RNA-regulatory pathway functions in vivo and contributes to mammalian development remains unknown. Here we find that YTHDF2 deficiency is partially permissive in mice and results in female-specific infertility. Using conditional mutagenesis, we demonstrate that YTHDF2 is autonomously required within the germline to produce MII oocytes that are competent to sustain early zygotic development. Oocyte maturation is associated with a wave of maternal RNA degradation, and the resulting relative changes to the MII transcriptome are integral to oocyte quality. The loss of YTHDF2 results in the failure to regulate transcript dosage of a cohort of genes during oocyte maturation, with enrichment observed for the YTHDF2-binding consensus and evidence of m6A in these upregulated genes. In summary, the m6A-reader YTHDF2 is an intrinsic determinant of mammalian oocyte competence and early zygotic development

NANOS2 is a sequence-specific mRNA-binding protein that promotes transcript degradation in spermatogonial stem cells

Summary: Spermatogonial stem cells (SSCs) sustain spermatogenesis and fertility throughout adult male life. The conserved RNA-binding protein NANOS2 is essential for the maintenance of SSCs, but its targets and mechanisms of function are not fully understood. Here, we generated a fully functional epitope-tagged Nanos2 mouse allele and applied the highly stringent cross-linking and analysis of cDNAs to define NANOS2 RNA occupancy in SSC lines. NANOS2 recognizes the AUKAAWU consensus motif, mostly found in the 3′ untranslated region of defined messenger RNAs (mRNAs). We find that NANOS2 is a regulator of key signaling and metabolic pathways whose dosage or activity are known to be critical for SSC maintenance. NANOS2 interacts with components of CCR4-NOT deadenylase complex in SSC lines, and consequently, NANOS2 binding reduces the half-lives of target transcripts. In summary, NANOS2 contributes to SSC maintenance through the regulation of target mRNA stability and key self-renewal pathways

Therapeutic limitations in tumor-specific CD8+ memory T cell engraftment

BACKGROUND: Adoptive immunotherapy with cytotoxic T lymphocytes (CTL) represents an alternative approach to treating solid tumors. Ideally, this would confer long-term protection against tumor. We previously demonstrated that in vitro-generated tumor-specific CTL from the ovalbumin (OVA)-specific OT-I T cell receptor transgenic mouse persisted long after adoptive transfer as memory T cells. When recipient mice were challenged with the OVA-expressing E.G7 thymoma, tumor growth was delayed and sometimes prevented. The reasons for therapeutic failures were not clear. METHODS: OT-I CTL were adoptively transferred to C57BL/6 mice 21 – 28 days prior to tumor challenge. At this time, the donor cells had the phenotypical and functional characteristics of memory CD8+ T cells. Recipients which developed tumor despite adoptive immunotherapy were analyzed to evaluate the reason(s) for therapeutic failure. RESULTS: Dose-response studies demonstrated that the degree of tumor protection was directly proportional to the number of OT-I CTL adoptively transferred. At a low dose of OT-I CTL, therapeutic failure was attributed to insufficient numbers of OT-I T cells that persisted in vivo, rather than mechanisms that actively suppressed or anergized the OT-I T cells. In recipients of high numbers of OT-I CTL, the E.G7 tumor that developed was shown to be resistant to fresh OT-I CTL when examined ex vivo. Furthermore, these same tumor cells no longer secreted a detectable level of OVA. In this case, resistance to immunotherapy was secondary to selection of clones of E.G7 that expressed a lower level of tumor antigen. CONCLUSIONS: Memory engraftment with tumor-specific CTL provides long-term protection against tumor. However, there are several limitations to this immunotherapeutic strategy, especially when targeting a single antigen. This study illustrates the importance of administering large numbers of effectors to engraft sufficiently efficacious immunologic memory. It also demonstrates the importance of targeting several antigens when developing vaccine strategies for cancer

Robust Models for Optic Flow Coding in Natural Scenes Inspired by Insect Biology

The extraction of accurate self-motion information from the visual world is a difficult problem that has been solved very efficiently by biological organisms utilizing non-linear processing. Previous bio-inspired models for motion detection based on a correlation mechanism have been dogged by issues that arise from their sensitivity to undesired properties of the image, such as contrast, which vary widely between images. Here we present a model with multiple levels of non-linear dynamic adaptive components based directly on the known or suspected responses of neurons within the visual motion pathway of the fly brain. By testing the model under realistic high-dynamic range conditions we show that the addition of these elements makes the motion detection model robust across a large variety of images, velocities and accelerations. Furthermore the performance of the entire system is more than the incremental improvements offered by the individual components, indicating beneficial non-linear interactions between processing stages. The algorithms underlying the model can be implemented in either digital or analog hardware, including neuromorphic analog VLSI, but defy an analytical solution due to their dynamic non-linear operation. The successful application of this algorithm has applications in the development of miniature autonomous systems in defense and civilian roles, including robotics, miniature unmanned aerial vehicles and collision avoidance sensors

Uncovering treatment burden as a key concept for stroke care: a systematic review of qualitative research

&lt;b&gt;Background&lt;/b&gt; Patients with chronic disease may experience complicated management plans requiring significant personal investment. This has been termed ‘treatment burden’ and has been associated with unfavourable outcomes. The aim of this systematic review is to examine the qualitative literature on treatment burden in stroke from the patient perspective.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods and findings&lt;/b&gt; The search strategy centred on: stroke, treatment burden, patient experience, and qualitative methods. We searched: Scopus, CINAHL, Embase, Medline, and PsycINFO. We tracked references, footnotes, and citations. Restrictions included: English language, date of publication January 2000 until February 2013. Two reviewers independently carried out the following: paper screening, data extraction, and data analysis. Data were analysed using framework synthesis, as informed by Normalization Process Theory. Sixty-nine papers were included. Treatment burden includes: (1) making sense of stroke management and planning care, (2) interacting with others, (3) enacting management strategies, and (4) reflecting on management. Health care is fragmented, with poor communication between patient and health care providers. Patients report inadequate information provision. Inpatient care is unsatisfactory, with a perceived lack of empathy from professionals and a shortage of stimulating activities on the ward. Discharge services are poorly coordinated, and accessing health and social care in the community is difficult. The study has potential limitations because it was restricted to studies published in English only and data from low-income countries were scarce.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; Stroke management is extremely demanding for patients, and treatment burden is influenced by micro and macro organisation of health services. Knowledge deficits mean patients are ill equipped to organise their care and develop coping strategies, making adherence less likely. There is a need to transform the approach to care provision so that services are configured to prioritise patient needs rather than those of health care systems