Empirical threshold values for quantitative trait mapping.

This book is one of our contemporary medical bibles. It needs no introduction; those who have frequent need of it know it very well, and those who use it less often seek it out on the library shelf when problems arise. The book is truly encyclopedic. Everything relevant discovered during the six-year intervals between publication finds its way into these pages. By today's standards, its 1,778 closely packed small-print pages are a bargain. The mutant gene is both hero and villain in this book. It is reponsible for the biochemical abnormality that results in disease, no matter how rare a given abnormality may be. By the same token, however, it is truly an experiment of nature, shedding light on fundamental metabolic sequences and biologic mechanisms. This volume, more than most, explains the contributions of the laboratory to clinical medicine. Each chapter seems to have been rewritten, so that the exciting

The Metabolic Basis Of Inherited Disease.

https://www.cell.com/molecular-plant/pdf/S1674-2052(15)00366-4.pdf

Amino Acid Catabolism in Plants

The growth of plants depends on continuous function of the meristems. Shoot meristems are responsible for all the post-embryonic aerial organs, such as leaves, stems and flowers. It has been assumed that the phytohormone cytokinin has a positive role in shoot meristem function. A severe reduction in the size of meristems in a mutant that is defective in all of its cytokinin receptors has provided compelling evidence that cytokinin is required for meristem activity. Here, we report a novel regulation of meristem activity, which is executed by the meristem-specific activation of cytokinins. The LONELY GUY (LOG) gene of rice is required to maintain meristem activity and its loss of function causes premature termination of the shoot meristem. LOG encodes a novel cytokinin-activating enzyme that works in the final step of bioactive cytokinin synthesis. Revising the long-held idea of multistep reactions, LOG directly converts inactive cytokinin nucleotides to the free-base forms, which are biologically active, by its cytokinin-specific phosphoribohydrolase activity. LOG messenger RNA is specifically localized in shoot meristem tips, indicating the activation of cytokinins in a specific developmental domain. We propose the fine-tuning of concentrations and the spatial distribution of bioactive cytokinins by a cytokinin-activating enzyme as a mechanism that regulates meristem activity.

Direct control of shoot meristem activity by a cytokinin-activating enzyme.

The phytohormone auxin plays critical roles during plant growth, many of which are mediated by the auxin response transcription factor (ARF) family. MicroRNAs (miRNAs), endogenous 21-nucleotide riboregulators, target several mRNAs implicated in auxin responses. miR160 targets ARF10 , ARF16 , and ARF17 , three of the 23 Arabidopsis thaliana ARF genes. Here, we describe roles of miR160-directed ARF17 posttranscriptional regulation. Plants expressing a miRNA-resistant version of ARF17 have increased ARF17 mRNA levels and altered accumulation of auxin-inducible GH3 -like mRNAs, YDK1/GH3.2 , GH3.3 , GH3.5 , and DFL1/GH3.6 , which encode auxin-conjugating proteins. These expression changes correlate with dramatic developmental defects, including embryo and emerging leaf symmetry anomalies, leaf shape defects, premature inflorescence development, altered phyllotaxy along the stem, reduced petal size, abnormal stamens, sterility, and root growth defects. These defects demonstrate the importance of miR160-directed ARF17 regulation and implicate ARF17 as a regulator of GH3 -like early auxin response genes. Many of these defects resemble phenotypes previously observed in plants expressing viral suppressors of RNA silencing and plants with mutations in genes important for miRNA biogenesis or function, providing a molecular rationale for phenotypes previously associated with more general disruptions of miRNA function.

/pdf/microrna-directed-regulation-of-arabidopsis-auxin-response-3ww5a0xywi.pdf

MicroRNA-Directed Regulation of Arabidopsis AUXIN RESPONSE FACTOR17 Is Essential for Proper Development and Modulates Expression of Early Auxin Response Genes

We describe a signaling pathway that mediates salt stress responses in Arabidopsis. The response is mechanistically related to endoplasmic reticulum (ER) stress responses described in mammalian systems. Such responses involve processing and relocation to the nucleus of ER membrane-associated transcription factors to activate stress response genes. The salt stress response in Arabidopsis requires a subtilisin-like serine protease (AtS1P), related to mammalian S1P and a membrane-localized b-ZIP transcription factor, AtbZIP17, a predicted type-II membrane protein with a canonical S1P cleavage site on its lumen-facing side and a b-ZIP domain on its cytoplasmic side. In response to salt stress, it was found that myc-tagged AtbZIP17 was cleaved in an AtS1P-dependent process. To show that AtS1P directly targets AtbZIP17, cleavage was also demonstrated in an in vitro pull-down assay with agarose bead-immobilized AtS1P. Under salt stress conditions, the N-terminal fragment of AtbZIP17 tagged with GFP was translocated to the nucleus. The N-terminal fragment bearing the bZIP DNA binding domain was also found to possess transcriptional activity that functions in yeast. In Arabidopsis, AtbZIP17 activation directly or indirectly upregulated the expression of several salt stress response genes, including the homeodomain transcription factor ATHB-7. Upregulation of these genes by salt stress was blocked by T-DNA insertion mutations in AtS1P and AtbZIP17. Thus, salt stress induces a signaling cascade involving the processing of AtbZIP17, its translocation to the nucleus and the upregulation of salt stress genes.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-313X.2007.03195.x

Salt stress responses in Arabidopsis utilize a signal transduction pathway related to endoplasmic reticulum stress signaling.

Stresses leading to the accumulation of misfolded proteins in the endoplasmic reticulum (ER) elicit a highly conserved ER stress response in plants called the unfolded protein response (UPR). While the response itself is well documented in plants, the components of the signaling pathway are less well known. We have identified three membrane-associated basic domain/leucine zipper (bZIP) factors in Arabidopsis thaliana that are candidates for ER stress sensors/transducers. One of these factors, bZIP28, an ER-resident transcription factor, is activated in response to treatment by tunicamycin (TM), an agent that blocks N-linked protein glycosylation. Following TM treatment, bZIP28 is processed, releasing its N-terminal, cytoplasm-facing domain, which is translocated to the nucleus. Expression of a truncated form of bZIP28, containing only the cytoplasmic domain of the protein, upregulated the expression of ER stress response genes in the absence of stress conditions. Thus, bZIP28 serves as a sensor/transducer in Arabidopsis to mediate ER stress responses related to UPR.

/pdf/an-endoplasmic-reticulum-stress-response-in-arabidopsis-is-2lcsojrqqw.pdf

An Endoplasmic Reticulum Stress Response in Arabidopsis Is Mediated by Proteolytic Processing and Nuclear Relocation of a Membrane-Associated Transcription Factor, bZIP28

Cytokinins and shoot development.

Summary

Critical developmental and gene expression profiles were charted during the formation of shoots from root explants in Arabidopsis tissue culture. Shoot organogenesis is a two-step process involving pre-incubation on an auxin-rich callus induction medium (CIM) during which time root explants acquire competence to form shoots during subsequent incubation on a cytokinin-rich shoot induction medium (SIM). At a histological level, the organization of shoot apical meristems (SAMs) appears to occur during incubation on SIM about the time of shoot commitment, i.e. the transition from hormone-dependent to hormone-independent shoot development. Genes involved in SAM formation, such as SHOOTMERISTEMLESS (STM) and CLAVATA1 (CLV1), were upregulated at about the time of shoot commitment, while WUSCHEL (WUS) was upregulated somewhat earlier. Genes required for STM expression, such as CUP-SHAPED COTYLEDON 1 and 2 (CUC1 and 2) were upregulated prior to shoot commitment. Gene expression patterns were determined for two GFP enhancer trap lines with tissue-specific expression in the SAM, including one line reporting on CUC1 expression. CUC1 was generally expressed in callus tissue during early incubation on SIM, but later CUC1 was expressed more locally in presumptive sites of shoot formation. In contrast, the expression pattern of the enhancer trap lines during zygotic embryogenesis was more localized to the presumptive SAM even in early stages of embryogenesis.

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-313X.2002.01479.x

Developmental events and shoot apical meristem gene expression patterns during shoot development in Arabidopsis thaliana

3-Methylcrotonyl-coenzyme A carboxylase (MCCase) is a mitochondrial biotin-containing enzyme whose metabolic function is not well understood in plants. In soybean (Glycine max) seedlings the organ-specific and developmentally induced changes in MCCase expression are regulated by mechanisms that control the accumulation of MCCase mRNA and the activity of the enzyme. During soybean cotyledon development, when seed-storage proteins are degraded, leucine (Leu) accumulation peaks transiently at 8 d after planting. The coincidence between peak MCCase expression and the decline in Leu content provides correlative evidence that MCCase is involved in the mitochondrial catabolism of Leu. Direct evidence for this conclusion was obtained from radiotracer metabolic studies using extracts from isolated mitochondria. These experiments traced the metabolic fate of [U-14C]Leu and NaH14CO3, the latter of which was incorporated into methylglutaconyl-coenzyme A (CoA) via MCCase. These studies directly demonstrate that plant mitochondria can catabolize Leu via the following scheme: Leu → α-ketoisocaproate → isovaleryl-CoA → 3-methylcrotonyl-CoA → 3-methylglutaconyl-CoA → 3-hydroxy-3-methylglutaryl-CoA → acetoacetate + acetyl-CoA. These findings demonstrate for the first time, to our knowledge, that the enzymes responsible for Leu catabolism are present in plant mitochondria. We conclude that a primary metabolic role of MCCase in plants is the catabolism of Leu.

http://www.plantphysiol.org/content/plantphysiol/118/4/1127.full.pdf

3-Methylcrotonyl-Coenzyme A Carboxylase Is a Component of the Mitochondrial Leucine Catabolic Pathway in Plants

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