The Deubiquitinating Enzyme AMSH1 and the ESCRT-III Subunit VPS2.1 Are Required for Autophagic Degradation in Arabidopsis

In eukaryotes, posttranslational modification by ubiquitin regulates the activity and stability of many proteins and thus influences a variety of developmental processes as well as environmental responses. Ubiquitination also plays a critical role in intracellular trafficking by serving as a signal for endocytosis. We have previously shown that the Arabidopsis thaliana ASSOCIATED MOLECULE WITH THE SH3 DOMAIN OF STAM3 (AMSH3) is a deubiquitinating enzyme (DUB) that interacts with ENDOSOMAL COMPLEX REQUIRED FOR TRANSPORT-III (ESCRT-III) and is essential for intracellular transport and vacuole biogenesis. However, physiological functions of AMSH3 in the context of its ESCRT-III interaction are not well understood due to the severe seedling lethal phenotype of its null mutant. In this article, we show that Arabidopsis AMSH1, an AMSH3-related DUB, interacts with the ESCRT-III subunit VACUOLAR PROTEIN SORTING2.1 (VPS2.1) and that impairment of both AMSH1 and VPS2.1 causes early senescence and hypersensitivity to artificial carbon starvation in the dark similar to previously reported autophagy mutants. Consistent with this, both mutants accumulate autophagosome markers and accumulate less autophagic bodies in the vacuole. Taken together, our results demonstrate that AMSH1 and the ESCRT-III-subunit VPS2.1 are important for autophagic degradation and autophagy-mediated physiological processes.     

Biodegradation of Malathion with Indigenous Acclimated Activated Sludge in Batch Mode and in Continuous-Flow Packed-Bed Reactor

Acclimated activated sludge was examined for its ability to degrade malathion with and without the presence of glucose as a potential cometabolite substrate. In this study, a packed-bed reactor (PBR) using three kinds of biofilm carriers was employed for efficient degradation of malathion. The results obtained indicate that microorganisms tested were able to degrade malathion. The observed degradation rate of the pesticide in the presence of glucose was the same as without glucose. The activated sludge was found to be able to use malathion as the sole phosphorus source. In contrast, the degradation ability of the activated sludge was lost when the pesticide was used as the sole source of sulfur. The degradation capacity of the PBR was higher than the performance obtained with the batch reactor. The reactor packed with crushed olive kernels exhibited the best performance, allowing a total removal of malathion (10 mg/dm³) within 12 h.     

The advantage of using a starch based non-Newtonian fluid to prepare micro sections

The breakage or distortion of cellular structures is one of the biggest problems in creating micro-sections for wood anatomical analyses in tree-ring as well as other branches of anatomical research. These broken or distorted structures cause artifacts in photomicrographs that require time consuming image manipulation or corrections prior to further analyses. The simple application of a cornstarch, water, and glycerol (CWG) solution (10:8:7 ratio), a so called non-Newtonian fluid to the surface of wooden specimen before sectioning improves the overall quality of the resulting micro-sections. In particular the problem of secondary cell walls splitting off the primary wall while sectioning is drastically reduced. The quality of the sections using this solution is comparable to that obtained from the more laborious and expensive paraffin embedding.     

p58IPK-Mediated Attenuation of the Proapoptotic PERK-CHOP Pathway Allows Malignant Progression upon Low Glucose

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Highlights? Transformation-associated glucose shortage triggers ER stress ? The ER stress acts as barrier to malignancy by triggering UPR-dependent apoptosis ? p58^IPK expression removes the UPR barrier by attenuating its PERK-CHOP branch ? This adaptive mechanism enables implementation of UPR cytoprotective features     

Telomere protection and TRF2 expression are enhanced by the canonical Wnt signalling pathway

The DNA‐binding protein TRF2 is essential for telomere protection and chromosome stability in mammals. We show here that TRF2 expression is activated by the Wnt/β‐catenin signalling pathway in human cancer and normal cells as well as in mouse intestinal tissues. Furthermore, β‐catenin binds to TRF2 gene regulatory regions that are functional in a luciferase transactivating assay. Reduced β‐catenin expression in cancer cells triggers a marked increase in telomere dysfunction, which can be reversed by TRF2 overexpression. We conclude that the Wnt/β‐catenin signalling pathway maintains a level of TRF2 critical for telomere protection. This is expected to have an important role during development, adult stem cell function and oncogenesis.     

Efficacy of anakinra in gouty arthritis: a retrospective study of 40 cases

Introduction

Gout is a common arthritis that occurs particularly in patients who frequently have associated comorbidities that limit the use of conventional therapies. The main mechanism of crystal-induced inflammation is interleukin-1 production by activation of the inflammasome. We aimed to evaluate the efficacy and tolerance of anakinra in gouty patients.

Methods

We conducted a multicenter retrospective review of patients receiving anakinra for gouty arthritis. We reviewed the response to treatment, adverse events and relapses.

Results

We examined data for 40 gouty patients (32 men; mean age 60.0 ± 13.9 years) receiving anakinra. Mean disease duration was 8.7 ± 8.7 years. All patients showed contraindications to and/or failure of at least two conventional therapies. Most (36; 90%) demonstrated good response to anakinra. Median pain on a 100-mm visual analog scale was rapidly decreased (73.5 (70.0 to 80.0) to 25.0 (20.0 to 32.5) mm, P <0.0001), as was median C-reactive protein (CRP) level (130.5 (55.8 to 238.8) to 16.0 (5.0 to 29.5) mg/l, P <0.0001). After a median follow-up of 7.0 (2.0 to 13.0) months, relapse occurred in 13 patients after a median delay of 15.0 (10.0 to 70.0) days. Seven infectious events, mainly with long-term use of anakinra, were noted.

Conclusions

Anakinra may be efficient in gouty arthritis, is relatively well tolerated with short-term use, and could be a relevant option in managing gouty arthritis when conventional therapies are ineffective or contraindicated. Its long-term use could be limited by infectious complications.     

Predictors of Chikungunya rheumatism: a prognostic survey ancillary to the TELECHIK cohort study

Introduction

Long-lasting relapsing or lingering rheumatic musculoskeletal pain (RMSP) is the hallmark of Chikungunya virus (CHIKV) rheumatism (CHIK-R). Little is known on their prognostic factors. The aim of this prognostic study was to search the determinants of lingering or relapsing RMSP indicative of CHIK-R.

Methods

Three hundred and forty-six infected adults (age ≥ 15 years) having declared RMSP at disease onset were extracted from the TELECHIK cohort study, Reunion island, and analyzed using a multinomial logistic regression model. We also searched for the predictors of CHIKV-specific IgG titres, assessed at the time of a serosurvey, using multiple linear regression analysis.

Results

Of these, 111 (32.1%) reported relapsing RMSP, 150 (43.3%) lingering RMSP, and 85 (24.6%) had fully recovered (reference group) on average two years after acute infection. In the final model controlling for gender, the determinants of relapsing RMSP were the age 45-59 years (adjusted OR: 2.9, 95% CI: 1.0, 8.6) or greater or equal than 60 years (adjusted OR: 10.4, 95% CI: 3.5, 31.1), severe rheumatic involvement (fever, at least six joints plus four other symptoms) at presentation (adjusted OR: 3.6, 95% CI: 1.5, 8.2), and CHIKV-specific IgG titres (adjusted OR: 3.2, 95% CI: 1.8, 5.5, per one unit increase). Prognostic factors for lingering RMSP were age 45-59 years (adjusted OR: 6.4, 95% CI: 1.8, 22.1) or greater or equal than 60 years (adjusted OR: 22.3, 95% CI: 6.3, 78.1), severe initial rheumatic involvement (adjusted OR: 5.5, 95% CI: 2.2, 13.8) and CHIKV-specific IgG titres (adjusted OR: 6.2, 95% CI: 2.8, 13.2, per one unit increase). CHIKV specific IgG titres were positively correlated with age, female gender and the severity of initial rheumatic symptoms.

Conclusions

Our data support the roles of age, severity at presentation and CHIKV specific IgG titres for predicting CHIK-R. By identifying the prognostic value of the humoral immune response of the host, this work also suggest a significant contribution of the adaptive immune response to the physiopathology of CHIK-R and should help to reconsider the paradigm of this chronic infection primarily shifted towards the involvement of the innate immune response.     

Serum level of adiponectin is a surrogate independent biomarker of radiographic disease progression in early rheumatoid arthritis: results from the ESPOIR cohort

Introduction

Adipokines such as adiponectin, leptin, and visfatin/nicotinamide phosphoribosyltransferase (NAMPT) have recently emerged as pro-inflammatory mediators involved in the pathophysiology of rheumatoid arthritis (RA). We aimed to determine whether serum adipokine levels independently predicted early radiographic disease progression in early RA.

Methods

In total, 791 patients were included from the prospective Etude et Suivi des POlyarthrites Indifférenciées Récentes (ESPOIR) cohort who met the American College of Rheumatology-European League Against Rheumatism criteria for RA (n = 632) or had undifferentiated arthritis (UA) (n = 159). Enzyme-linked immunosorbent assay (ELISA) was used to assess baseline serum levels of adiponectin, leptin, and visfatin/NAMPT. In the RA group, we tested the association of serum adipokine levels and (a) baseline radiographic damage and (b) radiographic disease progression, defined as a change >0 or ≥5 in total Sharp-van der Heijde Score (∆SHS) between inclusion and 1 year (∆SHS ≥1 or rapid radiographic progression: ∆SHS ≥5), adjusting for confounders (age, sex, body-mass index, insulin resistance, C-reactive protein level, Disease Activity Score in 28 joints, Health Assessment Questionnaire score, autoantibody status, steroid use, and radiographic evidence of RA damage at inclusion).

Results

Adiponectin level was independently associated with baseline total SHS (adjusted β = 0.12; P = 0.006). It was also associated with ∆SHS ≥1 (adjusted odds ratio (aOR) = 1.84 (1.25 to 2.72)) involving erosive as well as narrowing disease progression (aOR = 1.73 (1.17 to 2.55) and 1.93 (1.04 to 3.57), respectively). Serum adiponectin level predicted ∆SHS ≥5 (aOR = 2.0 (1.14 to 3.52)). Serum leptin level was independently associated only with ∆SHS >0 (aOR = 1.59 (1.05 to 2.42)). Conversely, serum visfatin/NAMPT level and radiographic disease progression were unrelated. Considering the receiver-operated characteristic curves, the best adiponectin cut-offs were 4.14 μg/ml for ∆SHS ≥1 and 6.04 μg/ml for ∆SHS ≥5, with a good specificity (58% and 75% for ∆SHS ≥1 and ∆SHS ≥5, respectively) and high negative predictive values (75% and 92% for ∆SHS ≥1 or ∆SHS ≥5, respectively).

Conclusion

Serum adiponectin level is a simple useful biomarker associated with early radiographic disease progression in early RA, independent of RA-confounding factors and metabolic status.     

Two newly recognized species of Hemidactylus (Squamata,Gekkonidae) from the Arabian Peninsula?and Sinai,Egypt

A recent molecular phylogeny of the Arid clade of the genus Hemidactylus revealed that the recently described H. saba and two unnamed Hemidactylus species from Sinai, Saudi Arabia and Yemen form a well-supported monophyletic group within the Arabian radiation of the genus. The name ‘Hemidactylus saba species group’ is suggested for this clade. According to the results of morphological comparisons and the molecular analyses using two mitochondrial (12S and cytb) and four nuclear (cmos, mc1r, rag1, rag2) genes, the name Hemidactylus granosus Heyden, 1827 is resurrected from the synonymy of H. turcicus for the Sinai and Saudi Arabian species. The third species of this group from Yemen is described formally as a new species H. ulii sp. n. The phylogenetic relationships of the members of ‘Hemidactylus saba species group’ are evaluated and the distribution and ecology of individual species are discussed.     

A two-phase heuristic for the energy-efficient scheduling of independent tasks on computational grids

The sensitivity analysis of a Cellular Genetic Algorithm (CGA) with local search is used to design a new and faster heuristic for the problem of mapping independent tasks to a distributed system (such as a computer cluster or grid) in order to minimize makespan (the time when the last task finishes). The proposed heuristic improves the previously known Min-Min heuristic. Moreover, the heuristic finds mappings of similar quality to the original CGA but in a significantly reduced runtime (1,000 faster). The proposed heuristic is evaluated across twelve different classes of scheduling instances. In addition, a proof of the energy-efficiency of the algorithm is provided. This convergence study suggests how additional energy reduction can be achieved by inserting low power computing nodes to the distributed computer system. Simulation results show that this approach reduces both energy consumption and makespan.