Nucleotide-binding leucine-rich repeat receptors (NLRs) recognize pathogen effectors to mediate plant disease resistance often involving host cell death. Effectors escape NLR recognition through ...polymorphisms, allowing the pathogen to proliferate on previously resistant host plants. The powdery mildew effector AVRA13-1 is recognized by the barley NLR MLA13 and activates host cell death. We demonstrate here that a virulent form of AVRA13, called AVRA13-V2, escapes MLA13 recognition by substituting a serine for a leucine residue at the C-terminus. Counterintuitively, this substitution in AVRA13-V2 resulted in an enhanced MLA13 association and prevented the detection of AVRA13-1 by MLA13. Therefore, AVRA13-V2 is a dominant-negative form of AVRA13 and has likely contributed to the breakdown of Mla13 resistance. Despite this dominant-negative activity, AVRA13-V2 failed to suppress host cell death mediated by the MLA13 auto-active MHD variant. Neither AVRA13-1 nor AVRA13-V2 interacted with the MLA13 auto-active variant, implying that the binding moiety in MLA13 that mediates association with AVRA13-1 is altered after receptor activation. We also show that mutations in the MLA13 coiled-coil domain, which were thought to impair Ca 2+ channel activity and NLR function, instead resulted in MLA13 auto-active cell death. The data constitute an important step to define intermediate receptor conformations during NLR activation.
The GOSAFE study evaluates risk factors for failing to achieve good quality of life (QoL) and functional recovery (FR) in older patients undergoing surgery for colon and rectal cancer.
Patients age ...70 years and older undergoing major elective colorectal surgery were prospectively enrolled. Frailty assessment was performed and outcomes, including QoL (EQ-5D-3L) recorded (3/6 months postoperatively). Postoperative FR was defined as a combination of Activity of Daily Living ≥5 + Timed Up & Go test <20 seconds + MiniCog >2.
Prospective complete data were available for 625/646 consecutive patients (96.9%; 435 colon and 190 rectal cancer), 52.6% men, and median age was 79.0 years (IQR, 74.6-82.9 years). Surgery was minimally invasive in 73% of patients (321/435 colon; 135/190 rectum). At 3-6 months, 68.9%-70.3% patients experienced equal/better QoL (72.8%-72.9% colon, 60.1%-63.9% rectal cancer). At logistic regression analysis, preoperative Flemish Triage Risk Screening Tool ≥2 (3-month odds ratio OR, 1.68; 95% CI, 1.04 to 2.73;
= .034, 6-month OR, 1.71; 95% CI, 1.06 to 2.75;
= .027) and postoperative complications (3-month OR, 2.03; 95% CI, 1.20 to 3.42;
= .008, 6-month OR, 2.56; 95% CI, 1.15 to 5.68;
= .02) are associated with decreased QoL after colectomy. Eastern Collaborative Oncology Group performance status (ECOG PS) ≥2 is a strong predictor of postoperative QoL decline in the rectal cancer subgroup (OR, 3.81; 95% CI, 1.45 to 9.92;
= .006). FR was reported by 254/323 (78.6%) patients with colon and 94/133 (70.6%) with rectal cancer. Charlson Age Comorbidity Index ≥7 (OR, 2.59; 95% CI, 1.26 to 5.32;
= .009), ECOG ≥2 (OR, 3.12; 95% CI, 1.36 to 7.20;
= .007 colon; OR, 4.61; 95% CI, 1.45 to 14.63;
= .009 rectal surgery), severe complications (OR, 17.33; 95% CI, 7.30 to 40.8;
< .001), fTRST ≥2 (OR, 2.71; 95% CI, 1.40 to 5.25;
= .003), and palliative surgery (OR, 4.11; 95% CI, 1.29 to 13.07;
= .017) are risk factors for not achieving FR.
The majority of older patients experience good QoL and stay independent after colorectal cancer surgery. Predictors for failing to achieve these essential outcomes are now defined to guide patients' and families' preoperative counseling.
AbstractObjectiveOlder patients with cancer value functional outcomes as much as survival, but surgical studies lack functional recovery (FR) data. The value of a standardized frailty assessment has ...been confirmed, yet it's infrequently utilized due to time restrictions into everyday practice. The multicenter GOSAFE study was designed to (1) evaluate the trajectory of patients' quality of life (QoL) after cancer surgery (2) assess baseline frailty indicators in unselected patients (3) clarify the most relevant tools in predicting FR and clinical outcomes. This is a report of the study design and baseline patient evaluations. Materials & MethodsGOSAFE prospectively collected a baseline multidimensional evaluation before major elective surgery in patients (≥70 years) from 26 international units. Short−/mid−/long-term surgical outcomes were recorded with QoL and FR data. Results1003 patients were enrolled in a 26-month span. Complete baseline data were available for 977(97.4%). Median age was 78 years (range 70–94); 52.8% males. 968(99%) lived at home, 51.6% without caregiver. 54.4% had ≥ 3 medications, 5.9% none. Patients were dependent (ADL < 5) in 7.9% of the cases. Frailty was either detected by G8 ≤ 14(68.4%), fTRST ≥ 2(37.4%), TUG > 20 s (5.2%) or ASAIII-IV (48.8%). Major comorbidities (CACI > 6) were detected in 36%; 20.9% of patients had cognitive impairment according to Mini-Cog. ConclusionThe GOSAFE showed that frailty is frequent in older patients undergoing cancer surgery. QoL and FR, for the first time, are going to be primary outcomes of a real-life observational study. The crucial role of frailty assessment is going to be addressed in the ability to predict postoperative outcomes and to correlate with QoL and FR.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The 16S rRNA mitochondrial gene was used to reconstruct the relationships among 10 heteronemertean species (subclass Heteronemertea, phylum Nemertea); Lineus ruber and L. viridis are represented by ...more than one specimen to assess intraspecific variation in these enigmatic species, and the analysis includes in total 14 terminal taxa incorporating one palaeonemertean species (Tubulanus annulatus) for outgroup rooting. The aligned sequences were subjected to maximum parsimony, maximum-likelihood, and neighbor-joining analyses to estimate the phylogenetic relationship of the species. The results were concordant from all analyses and indicate that neither Lineus nor Micrura are monophyletic taxa, and that there is no support from a phylogenetic point of view to establish the monotypic genus Riseriellus.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Maggot is an alternative to fish meal because it has a fairly high protein content, is easy to cultivate and is able to decompose organic waste into its own food. The better the quality of the maggot ...growing media, the higher the maggot production will be . Vegetable, fruit and food processing industrial waste is an organic waste that is commonly encountered but its nutritional quality is low. To improve the nutritional quality, fermentation was carried out using local microorganisms (MOL). The purpose of this study was to examine the effect of various types of vegetable, fruit and food processing industrial waste media and different fermentation times on the production of maggot (Hermetia illucens). This study was conducted experimentally using factorial randomized block design (RAK) method with 2 factors ( 3×3), namely factor 1 for various organic wastes (D1 = vegetable waste, D2 = fruit waste, D3 = food processing industrial waste) and factor 2 for fermentation time (L1 = 2 days, L2 = 4 days, L3 = 6 days), with 3 replicates. The parameters of this study consisted of biomass weight, feed consumption, waste reduction index/WRI, feed conversion efficiency/ECI, and survival rate/SR. The results of variance showed that organic waste and fermentation time had a very significant effect (p<0.01) on the parameters of maggot production. It was concluded that the production of maggot (Hermetia illucens) was best in the D1L1 treatment with a biomass weight of 1522.33 g, feed consumption 66.06%, WRI 2.20%, ECI 0.42%, and SR 89.52%.
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