The historical view of the adult brain as a static organ has shifted in the last few decades. We now know that the mature brain remains plastic and has some regeneration capacity after injury. The injured brain engages microglia/macrophages to clear cellular debris and fine-tune neurorestorative processes. However, microglia/macrophage activation can also hinder central nervous system (CNS) repair and expand tissue damage. One explanation for this dualistic role of microglia/macrophages in neurological recovery is their polarization into different phenotypes at different stages of injury. This perspective article highlights the specific roles of polarized microglia/macrophages in CNS repair after acute injuries. We propose that therapeutic approaches targeting cerebral inflammation should be shifted from complete microglia/macrophage suppression toward a subtler titration of the balance between various phenotypes. Recent breakthroughs in the identification of regulatory molecules that control this dramatic phenotypic shift are accelerating the pace of research towards curing brain disorders.
This study investigates the determinants of Chinese outward direct investment (ODI) and the extent to which three special explanations (capital market imperfections, special ownership advantages and institutional factors) need to be nested within the general theory of the multinational firm. We test our hypotheses using official Chinese ODI data collected between 1984 and 2001. We find Chinese ODI to be associated with high levels of political risk in, and cultural proximity to, host countries throughout, and with host market size and geographic proximity (1984 to 1991) and host natural resources endowments (1992 to 2001). We find strong support for the argument that aspects of the special theory help to explain the behaviour of Chinese MNEs.
A B S T R A C T PurposeCardiac dysfunction (CD) is a recognized risk associated with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer, especially when the treatment regimen includes anthracyclines. Given the demonstrated efficacy of trastuzumab, ongoing assessment of cardiac safety and identification of risk factors for CD are important for optimal patient care. Patients and MethodsIn National Surgical Adjuvant Breast and Bowel Project B-31, a phase III adjuvant trial, 1,830 patients who met eligibility criteria for initiation of trastuzumab were evaluated for CD. Recovery from CD was also assessed. A statistical model was developed to estimate the risk of severe congestive heart failure (CHF). Baseline patient characteristics associated with anthracyclinerelated decline in cardiac function were also identified. ResultsAt 7-year follow-up, 37 (4.0%) of 944 patients who received trastuzumab experienced a cardiac event (CE) versus 10 (1.3%) of 743 patients in the control arm. One cardiac-related death has occurred in each arm of the protocol. A Cardiac Risk Score, calculated using patient age and baseline left ventricular ejection fraction (LVEF) by multiple-gated acquisition scan, statistically correlates with the risk of a CE. After stopping trastuzumab, the majority of patients who experienced CD recovered LVEF in the normal range, although some decline from baseline often persists. Only two CEs occurred more than 2 years after initiation of trastuzumab. ConclusionThe late development of CHF after the addition of trastuzumab to paclitaxel after doxorubicin/ cyclophosphamide chemotherapy is uncommon. The risk versus benefit of trastuzumab as given in this regimen remains strongly in favor of trastuzumab.
Severe traumatic brain injury (TBI) elicits destruction of both gray and white matter, which is exacerbated by secondary proinflammatory responses. Although white matter injury (WMI) is strongly correlated with poor neurological status, the maintenance of white matter integrity is poorly understood, and no current therapies protect both gray and white matter. One candidate approach that may fulfill this role is inhibition of class I/II histone deacetylases (HDACs). Here we demonstrate that the HDAC inhibitor Scriptaid protects white matter up to 35 d after TBI, as shown by reductions in abnormally dephosphorylated neurofilament protein, increases in myelin basic protein, anatomic preservation of myelinated axons, and improved nerve conduction. Furthermore, Scriptaid shifted microglia/ macrophage polarization toward the protective M2 phenotype and mitigated inflammation. In primary cocultures of microglia and oligodendrocytes, Scriptaid increased expression of microglial glycogen synthase kinase 3 beta (GSK3β), which phosphorylated and inactivated phosphatase and tensin homologue (PTEN), thereby enhancing phosphatidylinositide 3-kinases (PI3K)/Akt signaling and polarizing microglia toward M2. The increase in GSK3β in microglia and their phenotypic switch to M2 was associated with increased preservation of neighboring oligodendrocytes. These findings are consistent with recent findings that microglial phenotypic switching modulates white matter repair and axonal remyelination and highlight a previously unexplored role for HDAC activity in this process. Furthermore, the functions of GSK3β may be more subtle than previously thought, in that GSK3β can modulate microglial functions via the PTEN/PI3K/Akt signaling pathway and preserve white matter homeostasis. Thus, inhibition of HDACs in microglia is a potential future therapy in TBI and other neurological conditions with white matter destruction.T raumatic brain injury (TBI) often leads to catastrophic neurological disabilities and sometimes ends in death (1). TBI results not only in gray matter damage, but also in severe white matter injury (WMI), thereby disrupting signal transmission and eliciting poor functional outcomes (2, 3). WMI in TBI patients is strongly correlated with neurological deficits, and diffusion tensor imaging of white matter offers prognostic value for neurological status (2-4). At present, there are no satisfactory therapies to protect TBI patients against either gray matter injury or WMI. Furthermore, most preclinical TBI studies greatly emphasize gray matter over white matter, which may contribute to the many disappointing results in clinical trials to date (5).Previous studies have shown that histone deacetylase (HDAC) inhibitors mitigate WMI after ischemia (6, 7). HDACs allow DNA to be wrapped more tightly around histones, thereby blocking gene transcription and acting in opposition to histone acetyltransferases that promote gene transcription (8, 9). Some HDAC inhibitors preferentially promote the transcription of neuroprotective genes. We...
Long-term feeding of adenine to rats produced metabolic abnormalities resembling chronic renal failure in humans. Among the disturbances produced were azotemia, accumulation of uremic toxins, metabolic imbalances of amino acids and electrolytes, and hormonal imbalances. The pathological findings in the kidneys of these experimental rats revealed lesions of proximal tubules, of some distal tubules and of glomeruli. Contracted kidneys were found in the rats with severe perturbations. Our results suggest that long-term adenine feeding provides a model which would be useful to study chronic renal failure.
CottonGen (http://www.cottongen.org) is a curated and integrated web-based relational database providing access to publicly available genomic, genetic and breeding data for cotton. CottonGen supercedes CottonDB and the Cotton Marker Database, with enhanced tools for easier data sharing, mining, visualization and data retrieval of cotton research data. CottonGen contains annotated whole genome sequences, unigenes from expressed sequence tags (ESTs), markers, trait loci, genetic maps, genes, taxonomy, germplasm, publications and communication resources for the cotton community. Annotated whole genome sequences of Gossypium raimondii are available with aligned genetic markers and transcripts. These whole genome data can be accessed through genome pages, search tools and GBrowse, a popular genome browser. Most of the published cotton genetic maps can be viewed and compared using CMap, a comparative map viewer, and are searchable via map search tools. Search tools also exist for markers, quantitative trait loci (QTLs), germplasm, publications and trait evaluation data. CottonGen also provides online analysis tools such as NCBI BLAST and Batch BLAST.
BackgroundTheobroma cacao L. cultivar Matina 1-6 belongs to the most cultivated cacao type. The availability of its genome sequence and methods for identifying genes responsible for important cacao traits will aid cacao researchers and breeders.ResultsWe describe the sequencing and assembly of the genome of Theobroma cacao L. cultivar Matina1-6. The genome of the Matina 1-6 cultivar is 445 Mbp, which is significantly larger than a sequenced Criollo cultivar, and more typical of other cultivars. The chromosome-scale assembly, version 1.1, contains 711 scaffolds covering 346.0 Mbp, with a contig N50 of 84.4 kbp, a scaffold N50 of 34.4 Mbp, and an evidence-based gene set of 29,408 loci. Version 1.1 has 10x the scaffold N50 and 4x the contig N50 as Criollo, and includes 111 Mb more anchored sequence. The version 1.1 assembly has 4.4% gap sequence, while Criollo has 10.9%. Through a combination of haplotype, association mapping and gene expression analyses, we leverage this robust reference genome to identify a promising candidate gene responsible for pod color variation. We demonstrate that green/red pod color in cacao is likely regulated by the R2R3 MYB transcription factor TcMYB113, homologs of which determine pigmentation in Rosaceae, Solanaceae, and Brassicaceae. One SNP within the target site for a highly conserved trans-acting siRNA in dicots, found within TcMYB113, seems to affect transcript levels of this gene and therefore pod color variation.ConclusionsWe report a high-quality sequence and annotation of Theobroma cacao L. and demonstrate its utility in identifying candidate genes regulating traits.
scite is a Brooklyn-based startup that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
334 Leonard St
Brooklyn, NY 11211
Copyright © 2023 scite Inc. All rights reserved.
Made with 💙 for researchers