Conservative versus Surgical Treatment of Pneumatosis Intestinalis: Experience from a Multidisciplinary Center.

BACKGROUND Pneumatosis intestinalis (PI) is an uncommon condition that is not specific to any particular disease. Currently, there is no specific clinical guideline for treating and diagnosing PI. Furthermore, there are numerous causes of PI, which makes it difficult for clinicians - internal medicine physicians as well as surgeons - to take a clinical approach to diagnosis and treatment. CASE REPORT We present 3 clinical scenarios with PI. In the first patient there was a solitary image of PI, which was treated successfully with parenteral nutrition and intravenous antibiotics, and he was discharged after 5 days. The other 2 cases, which involve gas in the hepatic portal vein (HPVG), were handled in 2 distinct ways: surgically and conservatively. One needed diagnostic laparoscopy with necrotic segmentectomy and was discharged from the hospital on postoperative day 16. The last patient, received resuscitation treatment due to severe comorbidities and inability to tolerate surgery. After 3 days, abdominal CT scan revealed no signs of remaining PI. However, the patient was terminally discharged after 7 weeks of treatment due to septic shock caused by sacrococcygeal ulcer and urinary tract infection. By drawing comparisons among these 3 scenarios, we aim to highlight certain indicators for conservative treatment success. CONCLUSIONS PI with HPVG is a sign of severe prognosis, which often requires surgical intervention. However, the decision to manage conservatively or surgically depends on the patient's condition and other criteria such as peritonitis, free fluid in the abdominal cavity, and the presence of shock. Physicians should also weigh the benefits and risks of surgical intervention in critically ill patients.

Genomic evidence reveals SPA-regulated developmental and metabolic pathways in dark-grown Arabidopsis seedlings.

Photomorphogenesis is repressed in the dark mainly by an E3 ubiquitin ligase complex comprising CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) and four homologous proteins called SUPPRESSOR OF PHYA-105 (SPA1-SPA4) in Arabidopsis. This complex induces the ubiquitination and subsequent degradation of positively acting transcription factors (TFs; e.g. ELONGATED HYPOCOTYL (HY5), LONG HYPOCOTYL IN FAR-RED 1 (HFR1), PRODUCTION OF ANTHOCYANIN PIGMENT 1 (PAP1) and others] in the dark to repress photomorphogenesis. Genomic evidence showed a large number of genes regulated by COP1 in the dark, of which many are direct targets of HY5. However, the genomic basis for the constitute photomorphogenic phenotype of spaQ remains unknown. Here, we show that >7200 genes are differentially expressed in the spaQ background compared to wild-type in the dark. Comparison of the RNA sequencing (RNA-Seq) data between cop1 and spaQ revealed a large overlapping set of genes regulated by the COP1-SPA complex. In addition, many of the genes coordinately regulated by the COP1-SPA complex are also regulated by HY5 directly and indirectly. Taken together, our data reveal that SPA proteins repress photomorphogenesis by controlling gene expression in concert with COP1, likely through regulating the abundance of downstream TFs in light signaling pathways. Moreover, SPA proteins may function both in a COP1-dependent and -independent manner in regulating many biological processes and developmental pathways in Arabidopsis.

Molecular bases for the constitutive photomorphogenic phenotypes in Arabidopsis.

The transition from skotomorphogenesis to photomorphogenesis is regulated in part by the COP1/SPA complex and phytochrome-interacting factors (PIFs) in Arabidopsis The constitutive photomorphogenic (cop) phenotypes of cop1 and spaQ mutants have been shown to result from a high abundance of positively acting transcription factors. Here, we show that the four major PIF proteins are unstable in cop1 mutants and that overexpression of PIF1, PIF3, PIF4 and PIF5 suppresses cop1 phenotypes in the dark. A comparison of the transcriptome data among cop1, spaQ and pifQ reveals remarkably overlapping gene expression profiles with preferential regulation of PIF direct target genes. Additionally, HFR1 strongly inhibits the in vivo binding and transcriptional activation activity of PIF1 in the dark. Taken together, these data suggest that the cop phenotypes of the cop1 and spaQ mutants are due to a combination of the reduced level of PIFs, increased levels of positively acting transcription factors (e.g. HY5/HFR1) and the HFR1-mediated inhibition of PIF-targeted gene expression in the dark. This article has an associated 'The people behind the papers' interview.

Dynamic regulation of PIF5 by COP1-SPA complex to optimize photomorphogenesis in Arabidopsis.

Light signal provides the spatial and temporal information for plants to adapt to the prevailing environmental conditions. Alterations in light quality and quantity can trigger robust changes in global gene expression. In Arabidopsis thaliana, two groups of key factors regulating those changes in gene expression are CONSTITUTIVE PHOTOMORPHOGENESIS/DEETIOLATED/FUSCA (COP/DET/FUS) and a subset of basic helix-loop-helix transcription factors called PHYTOCHROME-INTERACTING FACTORS (PIFs). Recently, rapid progress has been made in characterizing the E3 ubiquitin ligases for the light-induced degradation of PIF1, PIF3 and PIF4; however, the E3 ligase(s) for PIF5 remains unknown. Here, we show that the CUL4COP1-SPA complex is necessary for the red light-induced degradation of PIF5. Furthermore, COP1 and SPA proteins stabilize PIF5 in the dark, but promote the ubiquitination and degradation of PIF5 in response to red light through the 26S proteasome pathway. Genetic analysis illustrates that overexpression of PIF5 can partially suppress both cop1-4 and spaQ seedling de-etiolation phenotypes under dark and red-light conditions. In addition, the PIF5 protein level cycles under both diurnal and constant light conditions, which is also defective in the cop1-4 and spaQ backgrounds. Both cop1-4 and spaQ show defects in diurnal growth pattern. Overexpression of PIF5 partially restores growth defects in cop1-4 and spaQ under diurnal conditions, suggesting that the COP1-SPA complex plays an essential role in photoperiodic hypocotyl growth, partly through regulating the PIF5 level. Taken together, our data illustrate how the CUL4COP1-SPA E3 ligase dynamically controls the PIF5 level to regulate plant development.

Phytochromes and Phytochrome Interacting Factors.

The basic helix-loop-helix domain-containing transcription factors that interact physically with the red and far-red light photoreceptors, phytochromes, are called PHYTOCHROME INTERACTING FACTORS (PIFs). In the last two decades, the phytochrome-PIF signaling module has been shown to be conserved from Physcomitrella patens to higher plants. Exciting recent studies highlight the discovery of at least four distinct kinases (PPKs, CK2, BIN2, and phytochrome itself) and four families of ubiquitin ligases (SCFEBF1/2, CUL3LRB, CUL3BOP, and CUL4COP1-SPA) that regulate PIF abundance both in dark and light conditions. This review discusses these recent discoveries with a focus on the central phytochrome signaling mechanisms that have a profound impact on plant growth and development in response to light.

Reciprocal proteasome-mediated degradation of PIFs and HFR1 underlies photomorphogenic development in Arabidopsis.

The phytochrome-mediated regulation of photomorphogenesis under red and far-red light conditions involves both positively and negatively acting factors. The positively acting factors (e.g. HY5/HFR1/LAF1 and others) are degraded in the dark to prevent photomorphogenesis. By contrast, the negatively acting factors (e.g. phytochrome-interacting factors or PIFs) are degraded in response to light to promote photomorphogenesis. Here, we show that the negatively acting factor PIF1 is also degraded in the dark by direct heterodimerization with the positively acting factor HFR1. Conversely, PIF1 also promotes the degradation of HFR1 in darkness. PIF1 enhances the poly-ubiquitylation of HFR1 by COP1 in vivo and in vitro In addition, the reciprocal co-degradation of PIF1 and HFR1 is dependent on the 26S proteasome pathway in vivo Genetic evidence shows that the hfr1 mutant partially suppresses the constitutive photomorphogenic phenotypes of cop1-6 pif1 and of the quadruple mutant pifq both in the dark and in far-red light conditions. Taken together, these data uncover a co-degradation mechanism between PIFs and HFR1 that underlies photomorphogenic development in Arabidopsis thaliana.