Periportal Edema as an Extrarenal Manifestation of Acute Pyelonephritis.

Acute pyelonephritis is a common infection of the upper urinary tract that affects approximately 250,000 adults in the United States. Individuals with acute pyelonephritis require hospitalization and intravenous antimicrobial therapy. Diagnoses of acute pyelonephritis are made on the basis of clinical and laboratory findings. Individuals with complex or severe acute pyelonephritis undergo contrast-enhanced computed tomography (CT) for the diagnosis and assessment of perirenal abnormalities. However, extrarenal manifestations, such as periportal edema and gallbladder wall thickening, may complicate the diagnostic process. We report the case of a 42-year-old woman who presented with fever, dysuria, and flank pain-the hallmarks of urosepsis. CT results confirmed acute pyelonephritis accompanied by periportal edema and elevated levels of hepatic enzymes and C-reactive protein. Despite antibiotic intervention, febrile episodes persisted for 4 days and abated over a fortnight. The patient's blood and urine cultures yielded negative results, which may be attributed to her prior antimicrobial treatment. Recognition of extrarenal signs in acute pyelonephritis is crucial for obtaining accurate diagnoses and understanding their clinical implications.

Rare Condition of Aberrant Arterial Supply to a Normal Lung: A Cases Series and Literature Review.

Herein, we describe an aberrant artery to a normal lung, focusing on its classification, embryological hypotheses, diagnostic methods, and treatment modalities. We present three cases of aberrant arterial supply to a normal lung in various age groups (51 years, 5 months, and 29 years). The cases presented symptoms ranging from hemoptysis to respiratory distress. Successful transarterial embolization was performed in the 5-month-old infant. In addition, we collected case reports published from 1962 to the present from the literature to compare the trends in management and variations in manifestations.

The Effects of a Mindfulness Meditation Program on Quality of Life in Cancer Outpatients: An Exploratory Study.

OBJECTIVE: Numerous studies have investigated the efficacy of mindfulness meditation (MM) in managing quality of life (QoL) in cancer populations, yet only a few have studied the Asian population. The aim of this exploratory study is to evaluate the effect of a MM program on the QoL outcomes in Taiwanese cancer outpatients. METHODS: Patients with various cancer diagnoses were enrolled and assigned to the MM group and usual care (UC) group. The meditation intervention consisted of 3 sessions held monthly. The outcomes of the whole intervention were measured using the World Health Organization Quality of Life (WHOQOL-BREF) instrument. RESULTS: A total of 35 participants in the MM group and 34 in the UC group completed the study. The results showed that the postintervention scores were significantly higher than the preintervention scores in the MM group. In the UC group, there was no significant difference between preintervention and postintervention scores, except for the lower environment domain scores. There was no significant difference between the follow-up scores and postintervention scores in the MM group, indicating that improvement can be maintained for 3 months after completing the MM course. CONCLUSIONS: The present study provides preliminary outcomes of the effects on the QoL in Taiwanese cancer patients. The results suggest that MM may serve as an effective mind-body intervention for cancer patients to improve their QoL, and the benefits can persist over a 3-month follow-up period. This occurred in a diverse cancer population with various cancer diagnoses, strengthening the possibility of general use.

Strategies for gene disruption in Drosophila.

Drosophila melanogaster has been a classic model organism for the studies of genetics. More than 15,000 Drosophila genes have been annotated since the entire genome was sequenced; however, many of them still lack functional characterization. Various gene-manipulating approaches in Drosophila have been developed for the function analysis of genes. Here, we summarize some representative strategies utilized for Drosophila gene targeting, from the unbiased ethyl methanesulfonate (EMS) mutagenesis and transposable element insertion, to insertional/replacement homologous recombination and site-specific nucleases such as the zinc-finger nuclease (ZFN), the transcription activator-like effector nuclease (TALEN) and the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 system. Specifically, we evaluate the pros and cons of each technique in a historical perspective. This review discuss important factors that should be taken into consideration for the selection of a strategy that best fits the specific needs of a gene knockout project.

The traditional Chinese medicine prescription patterns for migraine patients in Taiwan: a population-based study.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM), when given for symptom relief, has gained widespread popularity among migraine patients. The aim of this study is to analyze the utilization of TCM among migraine patients in Taiwan. MATERIALS AND METHODS: The usage, frequency of service, and the Chinese herbal products prescribed for migraine were evaluated using a representative sample of one million subjects selected at random from the 22 million beneficiaries of the National Health Insurance scheme of Taiwan. RESULTS: Overall, 89.3% (N=12,827) migraine patients utilized TCM and 24.2% of them sought TCM with the intention of treating their migraine-related symptoms. Migraine patients who are living in urban area and those with an episodic migraine pattern (<15 days/month) (aOR=3.18, 95% CI: 2.75-3.67) were more likely to be TCM users than those living in a rural area and those who suffered from chronic migraine (≥15 days/month) (aOR=1.00). Overall, 81.2% of TCM visits involved the prescription of a Chinese herbal remedy or remedies and Chuan-Xiong-Cha-Tiao-San, Jia-Wei-Xiao-Yao-San, Ge-Gen-Tang, Xue-Fu-Zhu-Yu-Tang, Ban-Xia-Bai-Zhu-Tian-Ma-Tang, Qing-Shang-Juan-Tong-Tang, Xiao-Chai-Hu-Tang, Tian-Ma-Gou-Teng-Yin, Bu-Zhong-Yi-Qi-Tang, and Tian-Wang-Bu-Xin-Dan were the ten most frequently prescribed formula for treating migraine based on syndrome differentiation. CONCLUSIONS: Chuan-Xiong-Cha-Tiao-San, which contains sedative and anti-inflammatory agents, is the most commonly prescribed Chinese herbal formula for the treatment of migraine-related phenomena.

ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase.

Autophagy is the primary cellular catabolic program activated in response to nutrient starvation. Initiation of autophagy, particularly by amino-acid withdrawal, requires the ULK kinases. Despite its pivotal role in autophagy initiation, little is known about the mechanisms by which ULK promotes autophagy. Here we describe a molecular mechanism linking ULK to the pro-autophagic lipid kinase VPS34. Following amino-acid starvation or mTOR inhibition, the activated ULK1 phosphorylates Beclin-1 on Ser 14, thereby enhancing the activity of the ATG14L-containing VPS34 complexes. The Beclin-1 Ser 14 phosphorylation by ULK is required for full autophagic induction in mammals and this requirement is conserved in Caenorhabditis elegans. Our study reveals a molecular link from ULK1 to activation of the autophagy-specific VPS34 complex and autophagy induction.

The Drosophila GOLPH3 homolog regulates the biosynthesis of heparan sulfate proteoglycans by modulating the retrograde trafficking of exostosins.

The exostosin (EXT) genes encode glycosyltransferases required for glycosaminoglycan chain polymerization in the biosynthesis of heparan sulfate proteoglycans (HSPGs). Mutations in the tumor suppressor genes EXT1 and EXT2 disturb HSPG biosynthesis and cause multiple osteochondroma (MO). How EXT1 and EXT2 traffic within the Golgi complex is not clear. Here, we show that Rotini (Rti), the Drosophila GOLPH3, regulates the retrograde trafficking of EXTs. A reduction in Rti shifts the steady-state distribution of EXTs to the trans-Golgi. These accumulated EXTs tend to be degraded and their re-entrance towards the route for polymerizing GAG chains is disengaged. Conversely, EXTs are mislocalized towards the transitional endoplasmic reticulum/cis-Golgi when Rti is overexpressed. Both loss of function and overexpression of rti result in incomplete HSPGs and perturb Hedgehog signaling. Consistent with Drosophila, GOLPH3 modulates the dynamic retention and protein stability of EXT1/2 in mammalian species. Our data demonstrate that GOLPH3 modulates the activities of EXTs, thus implicating a putative role for GOLPH3 in the formation of MO.

The Hedgehog signalling pathway regulates autophagy.

Autophagy is a highly conserved degradative process that removes damaged or unnecessary proteins and organelles, and recycles cytoplasmic contents during starvation. Autophagy is essential in physiological processes such as embryonic development but how autophagy is regulated by canonical developmental pathways is unclear. Here we show that the Hedgehog signalling pathway inhibits autophagosome synthesis, both in basal and in autophagy-induced conditions. This mechanism is conserved in mammalian cells and in Drosophila, and requires the orthologous transcription factors Gli2 and Ci, respectively. Furthermore, we identify that activation of the Hedgehog pathway reduces PERK levels, concomitant with a decrease in phosphorylation of the translation initiation factor eukaryotic initiation factor 2α, suggesting a novel target of this pathway and providing a possible link between Hedgehog signalling and autophagy.

Characterization of Oncidium 'Gower Ramsey' transcriptomes using 454 GS-FLX pyrosequencing and their application to the identification of genes associated with flowering time.

Oncidium 'Gower Ramsey' is a valuable and successful commercial orchid for the floriculture industry in Taiwan. However, no genome reference for entire sequences of the transcribed genes currently exists for Oncidium orchids, to facilitate the development of molecular biological studies and the breeding of these orchids. In this study, we generated Oncidium cDNA libraries for six different organs: leaves, pseudobulbs, young inflorescences, inflorescences, flower buds and mature flowers. We utilized 454-pyrosequencing technology to perform high-throughput deep sequencing of the Oncidium transcriptome, yielding >0.9 million reads with an average length of 328 bp, for a total of 301 million bases. De novo assembly of the sequences yielded 50,908 contig sequences with an average length of 493 bp from 796,463 reads and 120,219 singletons. The assembled sequences were annotated using BLAST, and a total of 12,757 and 13,931 unigene transcripts from the Arabidopsis and rice genomes were matched by TBLASTX, respectively. A Gene Ontology (GO) analysis of the annotated Oncidium contigs revealed that the majority of sequenced genes were associated with 'unknown molecular function', 'cellular process' and 'intracellular components'. Furthermore, a complete flowering-associated expressed sequence that included most of the genes in the photoperiod pathway and the 15 CONSTANS-LIKE (COL) homologs with the conserved CCT domain was obtained in this collection. These data revealed that the Oncidium expressed sequence tag (EST) database generated in this study has sufficient coverage to be used as a tool to investigate the flowering pathway and various other biological pathways in orchids. An OncidiumOrchidGenomeBase (OOGB) website has been constructed and is publicly available online (http://predictor.nchu.edu.tw/oogb/).

C/D class MADS box genes from two monocots, orchid (Oncidium Gower Ramsey) and lily (Lilium longiflorum), exhibit different effects on floral transition and formation in Arabidopsis thaliana.

We have characterized three C/D class MADS box genes from an orchid (Oncidium Gower Ramsey) and a lily (Lilium longiflorum). OMADS4 of orchid and LMADS10 of lily are C class gene orthologs, whereas OMADS2 of orchid is a putative D class gene ortholog. The identity of these three genes is further supported by the presence of conserved motifs in the C-terminal regions of the proteins. The mRNA for these three genes can be detected in flowers and is absent in vegetative leaves. In flowers, OMADS4 and LMADS10 show similar expression patterns, being specifically expressed in the stamens and carpels. The expression of OMADS2 is restricted to the stigmatic cavity and ovary of the carpel. The similarities of the expression patterns of OMADS4/LMADS10 and OMADS2 to those of C and D class genes, respectively, indicate that their transcriptional regulation is highly evolutionarily conserved in these monocot species. Yeast two-hybrid analysis indicates that both OMADS2 and OMADS4 form homodimers and heterodimers with each other. Similar interactions are observed for LMADS2 and LMADS10. Ectopic expression of LMADS10 causes extremely early flowering, terminal flower formation and conversion of the sepals into carpel-like structures, similar to ectopic expression of the lily D class gene LMADS2. In contrast, 35S::OMADS2 and 35S::OMADS4 cause only early or moderately early flowering in transgenic Arabidopsis plants without floral organ conversion. This result indicates that C/D class genes from the lily have stronger effects than those from the orchid in transgenic Arabidopsis, revealing possible functional diversification of C/D class genes from the two monocots in regulating floral transition and formation.

Autophagy takes flight in Drosophila.

Drosophila has been shown to be a powerful model to study autophagy, whose regulation involves a core machinery consisting of Atg proteins and upstream signaling regulators similar to those in yeast and mammals. The conserved role in degrading proteins and organelles gives autophagy an important function in coordinating several cellular processes as well as in a number of pathological conditions. This review summarizes key studies in Drosophila autophagy research and discusses potential questions that may lead to better understanding of the roles and regulation of autophagy in higher eukaryotes.

Characterization of the possible roles for B class MADS box genes in regulation of perianth formation in orchid.

To investigate sepal/petal/lip formation in Oncidium Gower Ramsey, three paleoAPETALA3 genes, O. Gower Ramsey MADS box gene5 (OMADS5; clade 1), OMADS3 (clade 2), and OMADS9 (clade 3), and one PISTILLATA gene, OMADS8, were characterized. The OMADS8 and OMADS3 mRNAs were expressed in all four floral organs as well as in vegetative leaves. The OMADS9 mRNA was only strongly detected in petals and lips. The mRNA for OMADS5 was only strongly detected in sepals and petals and was significantly down-regulated in lip-like petals and lip-like sepals of peloric mutant flowers. This result revealed a possible negative role for OMADS5 in regulating lip formation. Yeast two-hybrid analysis indicated that OMADS5 formed homodimers and heterodimers with OMADS3 and OMADS9. OMADS8 only formed heterodimers with OMADS3, whereas OMADS3 and OMADS9 formed homodimers and heterodimers with each other. We proposed that sepal/petal/lip formation needs the presence of OMADS3/8 and/or OMADS9. The determination of the final organ identity for the sepal/petal/lip likely depended on the presence or absence of OMADS5. The presence of OMADS5 caused short sepal/petal formation. When OMADS5 was absent, cells could proliferate, resulting in the possible formation of large lips and the conversion of the sepal/petal into lips in peloric mutants. Further analysis indicated that only ectopic expression of OMADS8 but not OMADS5/9 caused the conversion of the sepal into an expanded petal-like structure in transgenic Arabidopsis (Arabidopsis thaliana) plants.

Four orchid (Oncidium Gower Ramsey) AP1/AGL9-like MADS box genes show novel expression patterns and cause different effects on floral transition and formation in Arabidopsis thaliana.

Four AP1/AGL9 functional MADS box genes were characterized from the orchid (Oncidium Gower Ramsey). OMADS6 is a SEP3 ortholog, OMADS11 is a SEP1/2 ortholog, OMADS7 is an AGL6-like gene and OMADS10 is a putative paleoAP1 ortholog. The identity of these four genes was further supported by the presence of conserved motifs in the C-terminal regions of the proteins. OMADS6 showed an expression pattern different from SEP3 orthologs, with expression in the sepal, petal, lip and carpel, and was barely detected in the stamen. The expression pattern for OMADS11 was similar to OMADS6 and different from SEP1/2 orthologs since its expression was undetectable in the stamen. The expression pattern for OMADS7 was nearly identical to OMADS6. The similarities in the expression patterns of the SEP/AGL6-like genes OMADS6, 11 and 7 indicated that their transcriptional regulation is highly evolutionarily conserved in the orchid. Unlike OMADS6/11/7, OMADS10 was only expressed in vegetative leaves and in the lip and carpel of mature flowers, which distinguishes it from most genes in the SQUA subfamily. Ectopic expression of OMADS6, 11 or 7 caused extremely early flowering, whereas 35S::OMADS10 only caused moderately early flowering in transgenic Arabidopsis plants. In addition, flower organ conversions, such as carpelloid sepals and staminoid petals, were observed in 35S::OMADS6 and carpelloid sepals were produced in 35S::OMADS7, while flower organ conversions were not observed in 35S::OMADS11 or 35S::OMADS10 transgenic flowers. This result reveals possible functional diversification of the orchid AP1/AGL9 genes OMADS6, 11, 7 and 10 in regulating flower transition and formation.

An Atg1/Atg13 complex with multiple roles in TOR-mediated autophagy regulation.

The TOR kinases are conserved negative regulators of autophagy in response to nutrient conditions, but the signaling mechanisms are poorly understood. Here we describe a complex containing the protein kinase Atg1 and the phosphoprotein Atg13 that functions as a critical component of this regulation in Drosophila. We show that knockout of Atg1 or Atg13 results in a similar, selective defect in autophagy in response to TOR inactivation. Atg1 physically interacts with TOR and Atg13 in vivo, and both Atg1 and Atg13 are phosphorylated in a nutrient-, TOR- and Atg1 kinase-dependent manner. In contrast to yeast, phosphorylation of Atg13 is greatest under autophagic conditions and does not preclude Atg1-Atg13 association. Atg13 stimulates both the autophagic activity of Atg1 and its inhibition of cell growth and TOR signaling, in part by disrupting the normal trafficking of TOR. In contrast to the effects of normal Atg13 levels, increased expression of Atg13 inhibits autophagosome expansion and recruitment of Atg8/LC3, potentially by decreasing the stability of Atg1 and facilitating its inhibitory phosphorylation by TOR. Atg1-Atg13 complexes thus function at multiple levels to mediate and adjust nutrient-dependent autophagic signaling.

Nutrient-dependent regulation of autophagy through the target of rapamycin pathway.

In response to nutrient deficiency, eukaryotic cells activate macroautophagy, a degradative process in which proteins, organelles and cytoplasm are engulfed within unique vesicles called autophagosomes. Fusion of these vesicles with the endolysosomal compartment leads to breakdown of the sequestered material into amino acids and other simple molecules, which can be used as nutrient sources during periods of starvation. This process is driven by a group of autophagy-related (Atg) proteins, and is suppressed by TOR (target of rapamycin) signalling under favourable conditions. Several distinct kinase complexes have been implicated in autophagic signalling downstream of TOR. In yeast, TOR is known to control autophagosome formation in part through a multiprotein complex containing the serine/threonine protein kinase Atg1. Recent work in Drosophila and mammalian systems suggests that this complex and its regulation by TOR are conserved in higher eukaryotes, and that Atg1 has accrued additional functions including feedback regulation of TOR itself. TOR and Atg1 also control the activity of a second kinase complex containing Atg6/Beclin 1, Vps (vacuolar protein sorting) 15 and the class III PI3K (phosphoinositide 3-kinase) Vps34. During autophagy induction, Vps34 activity is mobilized from an early endosomal compartment to nascent autophagic membranes, in a TOR- and Atg1-responsive manner. Finally, the well-known TOR substrate S6K (p70 ribosomal protein S6 kinase) has been shown to play a positive role in autophagy, which may serve to limit levels of autophagy under conditions of continuously low TOR activity. Further insight into these TOR-dependent control mechanisms may support development of autophagy-based therapies for a number of pathological conditions.