mab-31 and the TGF-β pathway act in the ray lineage to pattern C. elegans male sensory rays

<p>Abstract</p> <p>Background</p> <p><it>C. elegans </it>TGF-β-like Sma/Mab signaling pathway regulates both body size and sensory ray patterning. Most of the components in this pathway were initially identified by genetic screens based on the small body phenotype, and many of these mutants display sensory ray patterning defect. At the cellular level, little is known about how and where these components work although ray structural cell has been implicated as one of the targets. Based on the specific ray patterning abnormality, we aim to identify by RNAi approach additional components that function specifically in the ray lineage to elucidate the regulatory role of TGF-β signaling in ray differentiation.</p> <p>Result</p> <p>We report here the characterization of a new member of the Sma/Mab pathway, <it>mab-31</it>, recovered from a genome-wide RNAi screen. <it>mab-31 </it>mutants showed ray cell cluster patterning defect and mis-specification of the ray identity. <it>mab-31 </it>encodes a nuclear protein expressed in descendants of ray precursor cells impacting on the ray cell's clustering properties, orientation of cell division plane, and fusion of structural cells. Genetic experiments also establish its relationship with other Sma/Mab pathway components and transcription factors acting upstream and downstream of the signaling event.</p> <p>Conclusion</p> <p><it>mab-31 </it>function is indispensable in Sma/Mab signal recipient cells during sensory rays specification. Both <it>mab-31 </it>and <it>sma-6 </it>are required in ray lineage at the late larval stages. They act upstream of <it>C. elegans Pax-6 </it>homolog and repress its function. These findings suggested <it>mab-31 </it>is a key factor that can integrate TFG-β signals in male sensory ray lineage to define organ identity.</p

Word learning in bilingual children

In a 21st-century super-diverse world, young children are likely to speak different first languages which are not the majority language of society. For some children, preschool is one of the few environments where they experience this majority language. A pressing issue encountered by preschool teachers is how to communicate with these children and how to help these children acquire the majority language they need for a successful school entry. Building a repertoire of words in the majority language is one of the first steps. Strategies that monolingual children use to map words to their referents in the environment have been of interest for 60 years. However, less is known about the early development of word learning in bilingual children. This thesis, therefore, seeks to understand how monolingual and bilingual children utilise different strategies to learn words using experimental methods and look at how preschool teachers communicate with children in a preschool setting via naturalistic observation. The ultimate goal of this thesis is to identify and develop strategies that preschool teachers can use to foster children’s development of the majority language. In two experimental studies, this thesis examined (1) how monolingual and bilingual preschoolers learn words from speakers of different languages through mutual exclusivity and the acceptance of lexical overlap, and (2) whether and how socio-pragmatic cues influence monolingual and bilingual language learners’ learning of one-to-one and two-to-one word-object mappings through cross-situational statistics. In two observational studies, this thesis looked into whether and how preschool teachers in a UK setting communicated differently with monolingual preschoolers and preschoolers learning English as an additional language (EAL). The thesis also set out to identify the linguistic features of preschool talk that could predict preschoolers’, especially EAL children’s, language development. The findings of the experimental studies show a complex interaction between the different word-learning strategies and prior language experience, and the results suggest that word-learning strategies available to monolingual and bilingual learners are the same but used differently. The findings of the observational studies show that preschool teacher talk to EAL children, in terms of lexical diversity and syntactic complexity, affects the children’s development of English, suggesting that preschool teachers’ language use could scaffold and support EAL children’s acquisition of English. The findings of this thesis suggest that matching language input to EAL children’s English level and setting up learning situations that closely mimic those of bilingual word learning may be helpful strategies for preschool teachers to support EAL children’s English development

Central Neurocytoma: A Review of Clinical Management and Histopathologic Features.

Central neurocytoma (CN) is a rare, benign brain tumor often located in the lateral ventricles. CN may cause obstructive hydrocephalus and manifest as signs of increased intracranial pressure. The goal of treatment for CN is a gross total resection (GTR), which often yields excellent prognosis with a very high rate of tumor control and survival. Adjuvant radiosurgery and radiotherapy may be considered to improve tumor control when GTR cannot be achieved. Chemotherapy is also not considered a primary treatment, but has been used as a salvage therapy. The radiological features of CN are indistinguishable from those of other brain tumors; therefore, many histological markers, such as synaptophysin, can be very useful for diagnosing CNs. Furthermore, the MIB-1 Labeling Index seems to be correlated with the prognosis of CN. We also discuss oncogenes associated with these elusive tumors. Further studies may improve our ability to accurately diagnose CNs and to design the optimal treatment regimens for patients with CNs

The mTORC1/4E-BP pathway coordinates hemoglobin production with L-leucine availability

In multicellular organisms, the mechanisms by which diverse cell types acquire distinct amino acids and how cellular function adapts to their availability are fundamental questions in biology. We found that increased neutral essential amino acid (NEAA) uptake was a critical component of erythropoiesis. As red blood cells matured, expression of the amino acid transporter gene Lat3 increased, which increased NEAA import. Inadequate NEAA uptake by pharmacologic inhibition or RNAi-mediated knockdown of LAT3 triggered a specific reduction in hemoglobin production in zebrafish embryos and murine erythroid cells through the mTORC1 (mammalian target of rapamycin complex 1)/4E-BP (eukaryotic translation initiation factor 4E–binding protein) pathway. CRISPR-mediated deletion of members of the 4E-BP family in murine erythroid cells rendered them resistant to mTORC1 and LAT3 inhibition and restored hemoglobin production. These results identify a developmental role for LAT3 in red blood cells and demonstrate that mTORC1 serves as a homeostatic sensor that couples hemoglobin production at the translational level to sufficient uptake of NEAAs, particularly L-leucine

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

SATB2 is a Modulator of p63(alpha) in Cancer and Development

p63(alpha) belongs to the p53-family of proteins and has full-length (TA) as well as truncated ((delta)N) p63(alpha) isoforms. Previous studies have shown that TA and (delta)Np63(alpha) play multiple roles in cancer and development. In cancer, (delta)Np63(alpha)-mediated transcriptional repression promotes oncogenesis while transactivation by TAp63(alpha) is critical during development. Despite their importance, little is known regarding how TA or (delta)Np63(alpha) is regulated and factors influencing the function of p63(alpha) have yet to be identified. Here, I identify Special AT-rich Binding Protein 2 (SATB2) as a protein that forms a complex with and modulates the function of p63(alpha). SATB2 is detected in multiple head and neck squamous cell carcinoma (HNSCC) cell lines that also show overexpression of (delta)Np63(alpha). Histological analysis on tumor specimens revealed that SATB2 is predominantly expressed in advanced-stage HNSCC cancers. SATB2 increases DNA-binding capabilities of (delta)Np63(alpha), augmenting (delta)Np63(alpha) repression of apoptotic gene expression. Knockdown of SATB2 in HNSCC cells sensitizes cancer cells towards chemotherapy- and radiation-induced apoptosis. These results indicate that SATB2 functions as a co-factor and promotes the transrepression function of (delta)Np63(alpha) in HNSCC. In addition to examining the role of SATB2 in HNSCC, I also investigated the effect of SATB2 on the ability of TAp63(alpha) to induce gene expression. In particular, perp has been shown to be a critical downstream target of p63 during development. ChIP analysis revealed that while SATB2 increases TAp63(alpha)-binding to apoptotic gene promoters, SATB2 decreases TAp63(alpha) localization on the perp promoter and inhibits p63(alpha)-mediated perp induction. SATB2 more readily interacts with human disease-associated p63(alpha) mutations that are found in the SAM domain, further inhibiting transcriptional properties of these mutants. Together, my results suggest that SATB2 is an important modulator of p63(alpha) in cancer and development.Ph