Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 40
Filter
Add more filters

Country/Region as subject
Publication year range
1.
EMBO J ; 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39363036

ABSTRACT

The control of cell-cell communication via plasmodesmata (PD) plays a key role in plant development. In tree buds, low-temperature conditions (LT) induce a switch in plasmodesmata from a closed to an open state, which restores cell-to-cell communication in the shoot apex and releases dormancy. Using genetic and cell-biological approaches, we have identified a previously uncharacterized transcription factor, Low-temperature-Induced MADS-box 1 (LIM1), as an LT-induced, direct upstream activator of the gibberellic acid (GA) pathway. The LIM1-GA module mediates low temperature-induced plasmodesmata opening, by negatively regulating callose accumulation to promote dormancy release. LIM1 also activates expression of FT1 (FLOWERING LOCUS T), another LT-induced factor, with LIM1-FT1 forming a coherent feedforward loop converging on low-temperature regulation of gibberellin signaling in dormancy release. Mathematical modeling and experimental validation suggest that negative feedback regulation of LIM1 by gibberellin could play a crucial role in maintaining the robust temporal regulation of bud responses to low temperature. These results reveal genetic factors linking temperature control of cell-cell communication with regulation of seasonally-aligned growth crucial for adaptation of trees.

2.
J Surg Oncol ; 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39190497

ABSTRACT

BACKGROUND AND OBJECTIVES: Primary adrenal sarcoma (PAS) is an exceedingly rare malignancy with limited data available on its epidemiology, management, and outcomes. This study aimed to characterize the national incidence, treatment patterns, and survival of PAS utilizing a National Cancer Database. METHODS: The National Cancer Database was queried for patients diagnosed with primary adrenal tumors from 2004 to 2019. Cases with sarcoma histology were identified as PAS. Annual incidence trends, histological distribution, treatment modalities (surgery, chemotherapy, radiation therapy), perioperative outcomes, and overall survival (OS) were analyzed. RESULTS: Of 7213 primary adrenal tumor cases, 332 (4.6%) were PAS. The most common histological subtypes were leiomyosarcoma (37.3%), hemangiosarcoma (27.1%), and sarcoma not otherwise specified (6.0%). Most cases (71.7%) presented as locoregional disease. Treatment included surgery alone (47.8%), surgery plus chemotherapy and/or radiation (27.1%), chemotherapy/radiation alone (13.3%), or no treatment (13.9%). For surgical cases, the median length of stay was 5 days, the 30-day readmission rate was 3.36%, and the 30/90-day mortality rates were 3.65% and 9.90%, respectively. The 5-year OS rate for surgery alone was 43%, with a median OS of 34.6 months. For surgery with radiation/chemotherapy, the 5-year OS rate was 37.3%, with a median OS of 35.4 months. CONCLUSIONS: This largest analysis of PAS to date demonstrates that most cases present as locoregional disease amenable to surgical resection, with favorable outcomes. The role of adjuvant therapy remains unclear, as no significant survival difference was observed between surgery alone and multimodal treatment.

3.
HPB (Oxford) ; 26(5): 703-710, 2024 May.
Article in English | MEDLINE | ID: mdl-38443235

ABSTRACT

BACKGROUND: This study assessed the long-term quality of life (QOL) and priorities of pancreaticoduodenectomy (PD) survivors. METHODS: Survivors were surveyed via internet-based support groups. The relative importance of longevity, experience, costs, and QOL were assessed. RESULTS: The PD cohort (n = 247, 35%) was 60 ± 12 years, 71% female, and 93% white. With moderate agreement, patients ranked survival most important, followed by functional and emotional well-being; costs and experience were least important (W = 35.7%, p < 0.001). Well-being improved throughout survivorship (P-QOL: 39 ± 12 at ≤3 mo vs 43 ± 12 at >10 y, p = 0.170; M-QOL: 38 ± 13 at ≤3 mo vs 44 ± 16 at >10 y; p = 0.015) but remained below the general population (p < 0.001). PD patients with benign diagnoses ranked functional independence as most important (2.00 ± 1.13 vs 2.63 ± 1.19, p < 0.001, W = 41.1%); PD patients with malignant diagnoses regarded overall survival most important (2.10 ± 1.20 vs 1.82 ± 1.22, p < 0.16, W = 35.1%). The mean rank order of priorities remained concordant between short-term (<1 year) and long-term (>5 years) survivors. CONCLUSION: PD survivors experience long-term mental and physical health impairments, underscoring the importance of functional and emotional support. Survivors place paramount importance on overall survival, functional independence, and emotional well-being. Cancer survivors prioritize longevity, while survivors of chronic benign conditions prioritize functional independence.


Subject(s)
Pancreaticoduodenectomy , Quality of Life , Humans , Pancreaticoduodenectomy/adverse effects , Female , Male , Middle Aged , Aged , Time Factors , Surveys and Questionnaires , Survivors/psychology , Emotions , Mental Health , Functional Status , Treatment Outcome , Longevity
4.
Int J Mol Sci ; 22(17)2021 Aug 26.
Article in English | MEDLINE | ID: mdl-34502129

ABSTRACT

Size control is a fundamental question in biology, showing incremental complexity in plants, whose cells possess a rigid cell wall. The phytohormone auxin is a vital growth regulator with central importance for differential growth control. Our results indicate that auxin-reliant growth programs affect the molecular complexity of xyloglucans, the major type of cell wall hemicellulose in eudicots. Auxin-dependent induction and repression of growth coincide with reduced and enhanced molecular complexity of xyloglucans, respectively. In agreement with a proposed function in growth control, genetic interference with xyloglucan side decorations distinctly modulates auxin-dependent differential growth rates. Our work proposes that auxin-dependent growth programs have a spatially defined effect on xyloglucan's molecular structure, which in turn affects cell wall mechanics and specifies differential, gravitropic hypocotyl growth.


Subject(s)
Glucans/metabolism , Indoleacetic Acids/metabolism , Plant Cells/metabolism , Plant Development , Plant Physiological Phenomena , Xylans/metabolism , Arabidopsis/physiology , Cell Wall/metabolism , Fluorescent Antibody Technique , Gene Expression Regulation, Plant , Glucans/chemistry , Pisum sativum/physiology , Signal Transduction , Xylans/chemistry
5.
J Biol Chem ; 294(17): 6857-6870, 2019 04 26.
Article in English | MEDLINE | ID: mdl-30833326

ABSTRACT

Nonhost resistance of Arabidopsis thaliana against Phytophthora infestans, a filamentous eukaryotic microbe and the causal agent of potato late blight, is based on a multilayered defense system. Arabidopsis thaliana controls pathogen entry through the penetration-resistance genes PEN2 and PEN3, encoding an atypical myrosinase and an ABC transporter, respectively, required for synthesis and export of unknown indole compounds. To identify pathogen-elicited leaf surface metabolites and further unravel nonhost resistance in Arabidopsis, we performed untargeted metabolite profiling by incubating a P. infestans zoospore suspension on leaves of WT or pen3 mutant Arabidopsis plants. Among the plant-secreted metabolites, 4-methoxyindol-3-yl-methanol and S-(4-methoxy-indol-3-yl-methyl) cysteine were detected in spore suspensions recollected from WT plants, but at reduced levels from the pen3 mutant plants. In both whole-cell and microsome-based assays, 4-methoxyindol-3-yl-methanol was transported in a PEN3-dependent manner, suggesting that this compound is a PEN3 substrate. The syntheses of both compounds were dependent on functional PEN2 and phytochelatin synthase 1. None of these compounds inhibited mycelial growth of P. infestans in vitro Of note, exogenous application of 4-methoxyindol-3-yl methanol slightly elevated cytosolic Ca2+ levels and enhanced callose deposition in hydathodes of seedlings treated with a bacterial pathogen-associated molecular pattern (PAMP), flagellin (flg22). Loss of flg22-induced callose deposition in leaves of pen3 seedlings was partially reverted by the addition of 4-methoxyindol-3-yl methanol. In conclusion, we have identified a specific indole compound that is a substrate for PEN3 and contributes to the plant defense response against microbial pathogens.


Subject(s)
ATP-Binding Cassette Transporters/metabolism , Arabidopsis/metabolism , Flagellin/metabolism , Glucans/metabolism , Arabidopsis/microbiology , Calcium/metabolism , Cytosol/metabolism , Indoles/metabolism , Phytophthora infestans/isolation & purification , Plant Leaves/metabolism , Substrate Specificity
6.
Plant Cell ; 28(4): 930-48, 2016 04.
Article in English | MEDLINE | ID: mdl-27053424

ABSTRACT

Plant growth and architecture is regulated by the polar distribution of the hormone auxin. Polarity and flexibility of this process is provided by constant cycling of auxin transporter vesicles along actin filaments, coordinated by a positive auxin-actin feedback loop. Both polar auxin transport and vesicle cycling are inhibited by synthetic auxin transport inhibitors, such as 1-N-naphthylphthalamic acid (NPA), counteracting the effect of auxin; however, underlying targets and mechanisms are unclear. Using NMR, we map the NPA binding surface on the Arabidopsis thaliana ABCB chaperone TWISTED DWARF1 (TWD1). We identify ACTIN7 as a relevant, although likely indirect, TWD1 interactor, and show TWD1-dependent regulation of actin filament organization and dynamics and that TWD1 is required for NPA-mediated actin cytoskeleton remodeling. The TWD1-ACTIN7 axis controls plasma membrane presence of efflux transporters, and as a consequence act7 and twd1 share developmental and physiological phenotypes indicative of defects in auxin transport. These can be phenocopied by NPA treatment or by chemical actin (de)stabilization. We provide evidence that TWD1 determines downstream locations of auxin efflux transporters by adjusting actin filament debundling and dynamizing processes and mediating NPA action on the latter. This function appears to be evolutionary conserved since TWD1 expression in budding yeast alters actin polarization and cell polarity and provides NPA sensitivity.


Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , Indoleacetic Acids/metabolism , Tacrolimus Binding Proteins/metabolism , Actin Cytoskeleton/metabolism , Arabidopsis/genetics , Arabidopsis Proteins/genetics , Biological Transport/genetics , Biological Transport/physiology , Gene Expression Regulation, Plant/genetics , Gene Expression Regulation, Plant/physiology , Tacrolimus Binding Proteins/genetics
7.
BMC Surg ; 18(1): 86, 2018 Oct 16.
Article in English | MEDLINE | ID: mdl-30326866

ABSTRACT

BACKGROUND: THUNDERBEAT® (TB) (Olympus Medical Systems Corp., Tokyo, Japan) is a dynamic energy system device that simultaneously delivers ultrasonically generated frictional heat energy and electrically generated bipolar energy. TB is being routinely used in various operative procedures, however, less is known about its utility in liver resection. We, herein, report our early experience of using TB in open liver resection particularly in patients with normal or near-normal liver parenchyma. METHODS: We retrospectively reviewed the clinical characteristics, and evaluated the perioperative outcome of twenty-eight patients who underwent liver resection with TB, and twenty-four patients who underwent liver resection with basic procedure in our institution. The resection type was stratified into: major hepatectomy; resection of 3 or more than 3 Couinauds segments, and minor hepatectomy; resection of less than 3 Couinauds segments. RESULTS: Liver resection time (mean ± SD) in TB group with major hepatectomy was significantly shorter: 16.7 ± 8.8 compared to 62.8 ± 39.4 min in basic procedure group (P < 0.0001). Accordingly, the liver resection time (mean ± SD) in TB group with minor hepatectomy was also significantly shorter, 8.3 ± 2.9 min compared to 45.2 ± 23.9 min in liver resection with basic procedure (P < 0.001). No significant difference was observed between the groups in terms of intraoperative blood transfusion ratio, postoperative complication and postoperative liver dysfunction. CONCLUSION: TB as a new energy device can offer a safe, reliable and substantially rapid liver resection particularly in patients with normal or near-normal liver parenchyma.


Subject(s)
Hepatectomy/methods , Liver Neoplasms/surgery , Postoperative Complications/epidemiology , Adult , Aged , Aged, 80 and over , Blood Transfusion , Female , Humans , Japan , Male , Middle Aged , Retrospective Studies
8.
Plant Cell Physiol ; 58(10): 1601-1614, 2017 Oct 01.
Article in English | MEDLINE | ID: mdl-29016918

ABSTRACT

Different subclasses of ATP-binding cassette (ABC) transporters have been implicated in the transport of native variants of the phytohormone auxin. Here, the putative, individual roles of key members belonging to the ABCB, ABCD and ABCG families, respectively, are highlighted and the knowledge of their assumed expression and transport routes is reviewed and compared with their mutant phenotypes. Protein-protein interactions between ABC transporters and regulatory components during auxin transport are summarized and their importance is critically discussed. There is a focus on the functional interaction between members of the ABCB family and the FKBP42, TWISTED DWARF1, acting as a chaperone during plasma membrane trafficking of ABCBs. Further, the mode and relevance of functional ABCB-PIN interactions is diagnostically re-evaluated. A new nomenclature describing precisely the most likely ABCB-PIN interaction scenarios is suggested. Finally, available tools for the detection and prediction of ABC transporter interactomes are summarized and the potential of future ABC transporter interactome maps is highlighted.


Subject(s)
ATP-Binding Cassette Transporters/metabolism , Indoleacetic Acids/metabolism , Biological Transport , Gene Expression Regulation, Plant , Protein Binding , Protein Interaction Maps
9.
Ann Vasc Surg ; 40: 295.e9-295.e13, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27913123

ABSTRACT

Aneurysms of pancreatic arteries (PAs) are often found incidentally during evaluation of other abdominal pathology. Aneurysms involving multiple PAs are rarely reported in the literature. In case reports of PA aneurysm, inferior pancreaticoduodenal artery is the usual site of aneurysm occurrence. PA aneurysms can be treated surgically by aneurysm exclusion, excision, and by endovascular techniques. However, no clear consensus exists regarding treatment modality, leaving the surgeon to determine the most appropriate approach bearing in mind their experience, anatomical location of the aneurysm, involved artery, and urgency of the procedure. We report a rare PA aneurysm involving dorsal pancreatic artery (DPA) and anterior inferior pancreaticoduodenal artery (AIPDA) associated with celiac stenosis that was incidentally diagnosed in a patient with hepatic hemangioma. In addition, we reviewed data from the literature on patients with diffuse or multiple PA aneurysms and discuss the treatment modality in these rare variants. Both surgical and endovascular procedures are equally advocated in treatment of multiple PA aneurysms. In our report, we demonstrate a 2-stage surgical and endovascular treatment modality; DPA aneurysm that was not suitable for endovascular treatment was surgically resected and an iliohepatic bypass was made between left common iliac artery and AIPDA to ensure good hepatic perfusion. One month after the first procedure, AIPDA aneurysm was treated with endovascular embolization. Two-stage surgical and endovascular procedure may represent a useful strategy to treat aneurysms involving multiple PAs.


Subject(s)
Aneurysm/therapy , Arteries/surgery , Embolization, Therapeutic , Endovascular Procedures , Pancreas/blood supply , Saphenous Vein/transplantation , Aged , Aneurysm/diagnostic imaging , Aneurysm/physiopathology , Aneurysm/surgery , Aortography/methods , Arteries/diagnostic imaging , Arteries/physiopathology , Computed Tomography Angiography , Female , Humans , Iliac Artery/surgery , Incidental Findings , Ligation , Phlebography/methods , Regional Blood Flow , Saphenous Vein/diagnostic imaging , Treatment Outcome
10.
Plant J ; 83(5): 818-30, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26140668

ABSTRACT

Auxin and cadmium (Cd) stress play critical roles during root development. There are only a few reports on the mechanisms by which Cd stress influences auxin homeostasis and affects primary root (PR) and lateral root (LR) development, and almost nothing is known about how auxin and Cd interfere with root hair (RH) development. Here, we characterize rice osaux1 mutants that have a longer PR and shorter RHs in hydroponic culture, and that are more sensitive to Cd stress compared to wild-type (Dongjin). OsAUX1 expression in root hair cells is different from that of its paralogous gene, AtAUX1, which is expressed in non-hair cells. However, OsAUX1, like AtAUX1, localizes at the plasma membrane and appears to function as an auxin tranporter. Decreased auxin distribution and contents in the osaux1 mutant result in reduction of OsCyCB1;1 expression and shortened PRs, LRs and RHs under Cd stress, but may be rescued by treatment with the membrane-permeable auxin 1-naphthalene acetic acid. Treatment with the auxin transport inhibitors 1-naphthoxyacetic acid and N-1-naphthylphthalamic acid increased the Cd sensitivity of WT rice. Cd contents in the osaux1 mutant were not altered, but reactive oxygen species-mediated damage was enhanced, further increasing the sensitivity of the osaux1 mutant to Cd stress. Taken together, our results indicate that OsAUX1 plays an important role in root development and in responses to Cd stress.


Subject(s)
Cadmium/toxicity , Carrier Proteins/metabolism , Oryza/physiology , Plant Proteins/metabolism , Plant Roots/metabolism , Biological Transport , Cadmium/pharmacokinetics , Carrier Proteins/genetics , Cell Membrane/metabolism , Gene Expression Regulation, Plant , Glycolates/pharmacology , Hydroponics/methods , Indoleacetic Acids/metabolism , Mutation , Oryza/drug effects , Phthalimides/pharmacology , Plant Proteins/genetics , Plant Roots/growth & development , Plants, Genetically Modified , Stress, Physiological/drug effects
11.
Biochem Soc Trans ; 44(2): 663-73, 2016 Apr 15.
Article in English | MEDLINE | ID: mdl-27068986

ABSTRACT

The ABC (ATP-binding cassette) transporter family in higher plants is highly expanded compared with those of mammalians. Moreover, some members of the plant ABCB subfamily display very high substrate specificity compared with their mammalian counterparts that are often associated with multidrug resistance (MDR) phenomena. In this review we highlight prominent functions of plant and mammalian ABC transporters and summarize our knowledge on their post-transcriptional regulation with a focus on protein phosphorylation. A deeper comparison of regulatory events of human cystic fibrosis transmembrane conductance regulator (CFTR) and ABCB1 from the model plantArabidopsisreveals a surprisingly high degree of similarity. Both physically interact with orthologues of the FK506-binding proteins (FKBPs) that chaperon both transporters to the plasma membrane in an action that seems to involve Hsp90. Further both transporters are phosphorylated at regulatory domains that connect both nucleotide-binding folds. Taken together it appears that ABC transporters exhibit an evolutionary conserved but complex regulation by protein phosphorylation, which apparently is, at least in some cases, tightly connected with protein-protein interactions (PPI).

12.
Biochem Soc Trans ; 43(5): 966-74, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26517911

ABSTRACT

The ABC (ATP-binding cassette) transporter family in higher plants is highly expanded compared with those of mammalians. Moreover, some members of the plant ABC subfamily B (ABCB) display very high substrate specificity compared with their mammalian counterparts that are often associated with multi-drug resistance phenomena. In this review, we highlight prominent functions of plant and mammalian ABC transporters and summarize our knowledge on their post-transcriptional regulation with a focus on protein phosphorylation. A deeper comparison of regulatory events of human cystic fibrosis transmembrane conductance regulator (CFTR) and ABCB1 from the model plant Arabidopsis reveals a surprisingly high degree of similarity. Both physically interact with orthologues of the FK506-binding proteins that chaperon both transporters to the plasma membrane in an action that seems to involve heat shock protein (Hsp)90. Further, both transporters are phosphorylated at regulatory domains that connect both nt-binding folds. Taken together, it appears that ABC transporters exhibit an evolutionary conserved but complex regulation by protein phosphorylation, which apparently is, at least in some cases, tightly connected with protein-protein interactions (PPI).


Subject(s)
ATP-Binding Cassette Transporters/metabolism , Adenosine Triphosphate/metabolism , Plant Proteins/metabolism , ATP-Binding Cassette Transporters/genetics , Amino Acid Sequence , Animals , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Evolution, Molecular , Humans , Molecular Sequence Data , Phosphorylation , Plant Proteins/genetics , Sequence Homology, Amino Acid
13.
Plant Physiol ; 162(4): 1815-21, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23757404

ABSTRACT

Salicylic acid (SA) is central for the defense of plants to pathogens and abiotic stress. SA is synthesized in chloroplasts from chorismic acid by an isochorismate synthase (ICS1); SA biosynthesis is negatively regulated by autoinhibitory feedback at ICS1. Genetic studies indicated that the multidrug and toxin extrusion transporter ENHANCED DISEASE SUSCEPTIBILITY5 (EDS5) of Arabidopsis (Arabidopsis thaliana) is necessary for SA accumulation after biotic and abiotic stress, but so far it is not understood how EDS5 controls the biosynthesis of SA. Here, we show that EDS5 colocalizes with a marker of the chloroplast envelope and that EDS5 functions as a multidrug and toxin extrusion-like transporter in the export of SA from the chloroplast to the cytoplasm in Arabidopsis, where it controls the innate immune response. The location at the chloroplast envelope supports a model of the effect of EDS5 on SA biosynthesis: in the eds5 mutant, stress-induced SA is trapped in the chloroplast and inhibits its own accumulation by autoinhibitory feedback.


Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/physiology , Chloroplasts/metabolism , Membrane Transport Proteins/metabolism , Salicylic Acid/metabolism , Arabidopsis/drug effects , Arabidopsis/radiation effects , Arabidopsis Proteins/genetics , Biological Transport , Carbonyl Cyanide m-Chlorophenyl Hydrazone/pharmacology , Chloroplasts/genetics , Cytoplasm/genetics , Cytoplasm/metabolism , Immunity, Innate , Membrane Transport Proteins/genetics , Molecular Sequence Data , Mutation , Nigericin/pharmacology , Plants, Genetically Modified , Protoplasts/metabolism , Ultraviolet Rays
14.
Surg Today ; 44(8): 1584-7, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24062087

ABSTRACT

Parenchyma-sparing pancreatic resections have been reported increasingly in recent years; however, for multifocal diseases involving the head and the tail of the pancreas, total pancreatectomy is still the preferred procedure. The possible consequence of this procedure is loss of normal pancreatic parenchyma, resulting in insufficiency of pancreatic exocrine and endocrine functions. Various types of limited resection have been introduced for isolated or multiple pancreatic lesions, depending on the location of the tumor. Even for multifocal diseases, if the pancreatic body is spared, a middle-preserving pancreatectomy (MPP) can be performed to assure maximal pancreatic function and uncompromised quality of life. Yet, few papers have introduced the feasibility of MPP for a better outcome. This report describes a new surgical technique for MPP using an alternative approach for the remnant pancreas anastomosis. We used this technique successfully to remove a bifocal neoplasm: adenocarcinoma of the distal bile duct and mucinous cyst adenoma in the tail of the pancreas.


Subject(s)
Adenocarcinoma/surgery , Anastomosis, Surgical/methods , Bile Duct Neoplasms/surgery , Cystadenoma, Mucinous/surgery , Gastrostomy/methods , Neoplasms, Multiple Primary , Organ Sparing Treatments/methods , Pancreas/surgery , Pancreatectomy/methods , Pancreatic Neoplasms/surgery , Aged, 80 and over , Humans , Treatment Outcome
15.
Cancers (Basel) ; 16(4)2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38398150

ABSTRACT

Advancing cancer treatment relies on the rapid translation of new scientific discoveries to patient care. To facilitate this, an oncology biobank and data repository program, also referred to as the "Moonshot" program, was launched in 2021 within the Integrated Network Cancer Program of the Allegheny Health Network. A clinical data program (CDP) and biospecimen repository were established, and patient data and blood and tissue samples have been collected prospectively. To date, the study has accrued 2920 patients, predominantly female (61%) and Caucasian (90%), with a mean age of 64 ± 13 years. The most common cancer sites were the endometrium/uterus (12%), lung/bronchus (12%), breast (11%), and colon/rectum (11%). Of patients diagnosed with cancer, 34% were diagnosed at stage I, 25% at stage II, 26% at stage III, and 15% at stage IV. The CDP is designed to support our initiative in advancing personalized cancer research by providing a comprehensive array of patient data, encompassing demographic characteristics, diagnostic details, and treatment responses. The "Moonshot" initiative aims to predict therapy responses and clinical outcomes through cancer-related biomarkers. The CDP facilitates this initiative by fostering data sharing, enabling comparative analyses, and informing the development of novel diagnostic and therapeutic methods.

16.
Curr Biol ; 33(10): 2008-2023.e8, 2023 05 22.
Article in English | MEDLINE | ID: mdl-37146609

ABSTRACT

The exporter of the auxin precursor indole-3-butyric acid (IBA), ABCG36/PDR8/PEN3, from the model plant Arabidopsis has recently been proposed to also function in the transport of the phytoalexin camalexin. Based on these bonafide substrates, it has been suggested that ABCG36 functions at the interface between growth and defense. Here, we provide evidence that ABCG36 catalyzes the direct, ATP-dependent export of camalexin across the plasma membrane. We identify the leucine-rich repeat receptor kinase, QIAN SHOU KINASE1 (QSK1), as a functional kinase that physically interacts with and phosphorylates ABCG36. Phosphorylation of ABCG36 by QSK1 unilaterally represses IBA export, allowing camalexin export by ABCG36 conferring pathogen resistance. As a consequence, phospho-dead mutants of ABCG36, as well as qsk1 and abcg36 alleles, are hypersensitive to infection with the root pathogen Fusarium oxysporum, caused by elevated fungal progression. Our findings indicate a direct regulatory circuit between a receptor kinase and an ABC transporter that functions to control transporter substrate preference during plant growth and defense balance decisions.


Subject(s)
Arabidopsis Proteins , Arabidopsis , ATP-Binding Cassette Transporters/metabolism , Arabidopsis/metabolism , Thiazoles/metabolism , Phytoalexins , Arabidopsis Proteins/metabolism , Plant Diseases/microbiology , Gene Expression Regulation, Plant
17.
Fam Pract ; 29(5): 528-33, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22357578

ABSTRACT

BACKGROUND: The charity 'Health Partnership Nepal' is committed to both improving global health care and providing medical training links between Nepal and the UK. This paper analyses data gathered at rural health camps. AIM: To describe the demographics, diagnoses and treatments offered to people attending three rural health camps in Nepal during 2009. Design Cross-sectional study. Setting Three free health care camps established within the Nuwakot district of Nepal during April-May 2009. Camps were staffed by doctors including GPs, nurses and medical students from London and Kathmandu. METHODS: Attendees had treatment sheets completed which recorded their demographics, diagnoses and dispensed medications. RESULTS: The mean age of the 1903 consecutive patients attending was 42.8 years (range one month to 98 years) of whom 68.6% were female and 13.7% were children. The majority, 82.3%, were agricultural workers. For adults (n = 1574), the most frequent complaints were stomach pain 20.1%, musculoskeletal pain 19.3% and visual acuity problems 6.1%. Stomach pain was significantly more common in women than men [21.2% (236/1064) versus 14.5% (65/449) P < 0.01]. For children (n = 249), the most common diagnoses were helminthiasis 10.4%, conjunctivitis 7.6% and upper respiratory tract infection 7.2%. Overall, opthalmological, gastroenterological and rheumatological diagnoses were significantly more common in Nepalese than UK general practice patients. Of 1109 recorded prescriptions, the most common were multivitamins 23%, oral analgesics 15% and oral antibiotics 14%. CONCLUSIONS: There is a considerable unmet disease burden within rural districts of Nepal particularly for stomach pain, musculoskeletal pain and visual acuity problems. When planning similar rurally based health camps, we recommend recruiting GPs and ophthalmologists.


Subject(s)
Demography , Epidemiology , Health Status Indicators , Rural Health , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Male , Middle Aged , Nepal , Prescription Drugs/therapeutic use , Young Adult
18.
Sci Adv ; 8(49): eabq2047, 2022 Dec 09.
Article in English | MEDLINE | ID: mdl-36490331

ABSTRACT

Endoreplication is an evolutionarily conserved mechanism for increasing nuclear DNA content (ploidy). Ploidy frequently scales with final cell and organ size, suggesting a key role for endoreplication in these processes. However, exceptions exist, and, consequently, the endoreplication-size nexus remains enigmatic. Here, we show that prolonged tissue folding at the apical hook in Arabidopsis requires endoreplication asymmetry under the control of an auxin gradient. We identify a molecular pathway linking endoreplication levels to cell size through cell wall remodeling and stiffness modulation. We find that endoreplication is not only permissive for growth: Endoreplication reduction enhances wall stiffening, actively reducing cell size. The cell wall integrity kinase THESEUS plays a key role in this feedback loop. Our data thus explain the nonlinearity between ploidy levels and size while also providing a molecular mechanism linking mechanochemical signaling with endoreplication-mediated dynamic control of cell growth.

19.
Can Med Educ J ; 12(2): e112-e114, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33995731

ABSTRACT

The Coronavirus disease (COVID-19) pandemic continues to shut down colleges and universities including medical schools all over the world, thus pushing medical schools to seek e-learning to maintain continuity of curriculum. Although developed countries are comfortable learning through the internet, low-income countries like Nepal with limited experience in e-learning have used this lockdown as an opportunity to develop online classes. This crisis has clearly revealed the importance of e-learning in for medical educators in Nepal to disseminate knowledge beyond the restrictions of geography and other barriers.


La pandémie de la maladie à coronavirus (COVID-19) continue de provoquer la fermeture des collèges et des universités partout dans le monde, incitant les facultés de médecine à recourir à l'enseignement en ligne pour maintenir la continuité des programmes d'études. Tandis que les pays développés s'adaptent bien à l'enseignement en ligne, les pays à faible revenu comme le Népal, qui ont une expérience limitée de cette technologie, ont profité du confinement pour mettre au point des cours en ligne. La crise a mis en évidence l'importance de cette modalité d'enseignement pour les enseignants en médecine au Népal dans la mesure où elle leur permet de surmonter les contraintes géographiques et d'autres barrières à la diffusion des connaissances.

20.
Asian J Surg ; 44(12): 1510-1514, 2021 Dec.
Article in English | MEDLINE | ID: mdl-33865665

ABSTRACT

BACKGROUND/OBJECTIVE: Postoperative pancreatic fistula (POPF) leads to life-threatening complications after pancreaticoduodenectomy (PD). Pancreaticogastrostomy (PG) often adopted as a reconstruction technique after PD to prevent POPF. Delayed gastric emptying (DGE) following PD is the most common complication that compromises the quality of life. Subtotal stomach-preserving PD (SSPPD) preserves the pooling ability of the stomach and minimize the occurrence of DGE. This study aimed to describe our PG technique following SSPPD and evaluate the perioperative outcomes. METHODS: The study included patients who underwent PG following SSPPD from August 2013 to July 2020 at our institution. An invaginated PG was performed by one-layer eight interrupted sutures with a lost stent. Patients' demographics and perioperative outcomes were documented. RESULTS: This technique was applied in 72 patients with a median age of 75 years. The median operative time was 342 min. The clinically relevant POPF, DGE and post-pancreatectomy hemorrhage was 4 (5.6%), 5 (6.9%), and 10 (13.9%), respectively. Although the drain fluid amylase concentration on postoperative day 3 was significantly higher in clinically relevant POPF (CR-POPF) positive group (median, 2006 U/L vs. 74 U/L in CR-POPF negative group, p = 0.002), none of the risk factors including disease pathology, pancreatic duct diameter, texture of pancreas and excessive blood loss were significantly associated with CR-POPF. Other morbidity ≥ Clavien-Dindo classification II occurred in 29 patients (40.3%). The 90-days operative mortality was two (2.8%). CONCLUSIONS: This novel method of one-layer invaginated PG following SSPPD is safe and dependable procedure with acceptable morbidity and mortality.


Subject(s)
Pancreatectomy , Pancreaticoduodenectomy , Aged , Humans , Pancreas/surgery , Pancreaticoduodenectomy/adverse effects , Quality of Life , Stomach/surgery
SELECTION OF CITATIONS
SEARCH DETAIL