Exploring the source of TYLCV resistance in Nicotiana benthamiana

Tomato Yellow Leaf Curl Virus (TYLCV) is one of the most devastating pathogens of tomato, worldwide. It is vectored by the globally prevalent whitefly, Bemisia tabaci, and is asymptomatic in a wide range of plant species that act as a virus reservoir. The most successful crop protection for tomato in the field has been from resistance genes, of which five loci have been introgressed fromwild relatives. Of these, the Ty-1/Ty-3 locus, which encodes an RNA-dependent RNA polymerase 3 (RDR3), has been the most effective. Nevertheless, several TYLCV strains that break this resistance are beginning to emerge, increasing the need for new sources of resistance. Here we use segregation analysis and CRISPR-mediated gene dysfunctionalisation to dissect the differential response of two isolates of Nicotiana benthamiana to TYLCV infection. Our study indicates the presence of a novel non-RDR3, but yet to be identified, TYLCV resistance gene in a wild accession of N. benthamiana. This gene has the potential to be incorporated into tomatoes

Research on the Cultivation of Business English Talents and the Teaching Mode of Business English in Colleges for Nationalities

With the development of society, the strengthening of economic globalization and the deepening of reform and open-up, Business English teaching is attracting more and more attention. But Business English teaching in colleges for nationalities is still facing many problems, hinders the improvement of Business English teaching quality and the development of Business English. Starting from the connotation of Business English, this paper reveals the common problems existing in Business English teaching, analyzes the causes and puts forward some reform measures, in order to cultivate well-educated Business English talents for the ethnic areas

Evaluating Glucose Control With a Novel Composite Continuous Glucose Monitoring Index.

OBJECTIVE: The objective was to describe a novel composite continuous glucose monitoring index (COGI) and to evaluate its utility, in adults with type 1 diabetes, during hybrid closed-loop (HCL) therapy and multiple daily injections (MDI) therapy combined with real-time continuous glucose monitoring (CGM). METHODS: COGI consists of three key components of glucose control as assessed by CGM: Time in range (TIR), time below range (TBR), and glucose variability (GV) (weighted by 50%, 35% and 15%). COGI ranges from 0 to 100, where 1% increase of time 7.5-10%, had significantly higher COGI during 12 weeks of HCL compared to sensor-augmented pump therapy, mean (SD), 60.3 (8.6) versus 69.5 (6.9), P 7.5% to 9.9%, use of real-time CGM led to improved COGI, 49.8 (14.2) versus 58.2 (9.1), P < .0001. In MDI users with impaired awareness of hypoglycemia, use of real-time CGM led to improved COGI, 53.4 (12.2) versus 66.7 (11.1), P < .001. CONCLUSIONS: COGI summarizes three key aspects of CGM data into a concise metric that could be utilized to evaluate the quality of glucose control and to demonstrate the incremental benefit of a wide range of treatment modalities

Time spent in hypoglycemia according to age and time-of-day: Observations during closed-loop insulin delivery.

OBJECTIVE We aimed to assess whether percentage of time spent in hypoglycemia during closed-loop insulin delivery differs by age-group and time-of-day. METHODS We retrospectively analyzed data from hybrid closed-loop studies involving young children (2-7 years), children and adolescents (8-18 years), adults (19-59 years), and older adults (≥60 years) with type 1 diabetes. Main outcome was time spent in hypoglycemia <3.9mmol/l. Eight weeks of data for 88 participants were analyzed. RESULTS Median time spent in hypoglycemia over the 24-hour period was highest in children and adolescents (4.4%; [IQR 2.4-5.0]) and very young children (4.0% [3.4-5.2]), followed by adults (2.7% [1.7-4.0]), and older adults (1.8% [1.2-2.2]); p<0.001 for difference between age-groups. Time spent in hypoglycemia during nighttime (midnight-05:59) was lower than during daytime (06:00-23:59) across all age-groups. CONCLUSION Time in hypoglycemia was highest in the pediatric age-group during closed-loop insulin delivery. Hypoglycemia burden was lowest overnight across all age-groups

Metabolic Adaptation in Transplastomic Plants Massively Accumulating Recombinant Proteins

BACKGROUND: Recombinant chloroplasts are endowed with an astonishing capacity to accumulate foreign proteins. However, knowledge about the impact on resident proteins of such high levels of recombinant protein accumulation is lacking. METHODOLOGY/PRINCIPAL FINDINGS: Here we used proteomics to characterize tobacco (Nicotiana tabacum) plastid transformants massively accumulating a p-hydroxyphenyl pyruvate dioxygenase (HPPD) or a green fluorescent protein (GFP). While under the conditions used no obvious modifications in plant phenotype could be observed, these proteins accumulated to even higher levels than ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco), the most abundant protein on the planet. This accumulation occurred at the expense of a limited number of leaf proteins including Rubisco. In particular, enzymes involved in CO(2) metabolism such as nuclear-encoded plastidial Calvin cycle enzymes and mitochondrial glycine decarboxylase were found to adjust their accumulation level to these novel physiological conditions. CONCLUSIONS/SIGNIFICANCE: The results document how protein synthetic capacity is limited in plant cells. They may provide new avenues to evaluate possible bottlenecks in recombinant protein technology and to maintain plant fitness in future studies aiming at producing recombinant proteins of interest through chloroplast transformation

Day-and-night glycaemic control with closed-loop insulin delivery versus conventional insulin pump therapy in free-living adults with well controlled type 1 diabetes: an open-label, randomised, crossover study.

BACKGROUND: Tight control of blood glucose concentration in people with type 1 diabetes predisposes to hypoglycaemia. We aimed to investigate whether day-and-night hybrid closed-loop insulin delivery can improve glucose control while alleviating the risk of hypoglycaemia in adults with HbA1c below 7·5% (58 mmol/mol). METHODS: In this open-label, randomised, crossover study, we recruited adults (aged ≥18 years) with type 1 diabetes and HbA1c below 7·5% from Addenbrooke's Hospital (Cambridge, UK) and Medical University of Graz (Graz, Austria). After a 2-4 week run-in period, participants were randomly assigned (1:1), using web-based randomly permuted blocks of four, to receive insulin via the day-and-night hybrid closed-loop system or usual pump therapy for 4 weeks, followed by a 2-4 week washout period and then the other intervention for 4 weeks. Treatment interventions were unsupervised and done under free-living conditions. During the closed-loop period, a model-predictive control algorithm directed insulin delivery, and prandial insulin delivery was calculated with a standard bolus wizard. The primary outcome was the proportion of time when sensor glucose concentration was in target range (3·9-10·0 mmol/L) over the 4 week study period. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02727231, and is completed. FINDINGS: Between March 21 and June 24, 2016, we recruited 31 participants, of whom 29 were randomised. One participant withdrew during the first closed-loop period because of dissatisfaction with study devices and glucose control. The proportion of time when sensor glucose concentration was in target range was 10·5 percentage points higher (95% CI 7·6-13·4; p<0·0001) during closed-loop delivery compared with usual pump therapy (65·6% [SD 8·1] when participants used usual pump therapy vs 76·2% [6·4] when they used closed-loop). Compared with usual pump therapy, closed-loop delivery also reduced the proportion of time spent in hypoglycaemia: the proportion of time with glucose concentration below 3·5 mmol/L was reduced by 65% (53-74, p<0·0001) and below 2·8 mmol/L by 76% (59-86, p<0·0001). No episodes of serious hypoglycaemia or other serious adverse events occurred. INTERPRETATION: Use of day-and-night hybrid closed-loop insulin delivery under unsupervised, free-living conditions for 4 weeks in adults with type 1 diabetes and HbA1c below 7·5% is safe and well tolerated, improves glucose control, and reduces hypoglycaemia burden. Larger and longer studies are warranted. FUNDING: Swiss National Science Foundation (P1BEP3_165297), JDRF, UK National Institute for Health Research Cambridge Biomedical Research Centre, and Wellcome Strategic Award (100574/Z/12/Z)

Infections sexuellement transmissibles à Chlamydia trachomatis

Depuis quelques années, le diagnostic d’infection sexuellement transmissible à Chlamydia trachomatis est de plus en plus souvent posé. Les infections à Chlamydia, qui touchent principalement les jeunes femmes, sont redoutées en raison du risque d’infection ascendante (maladie inflammatoire pelvienne) et des complications potentielles sévères, telles que grossesse extra-utérine et stérilité. Même si ces troubles sont beaucoup plus rares que ce que l’on pensait, la prise en charge des personnes atteintes doit être améliorée

Hybrid closed‐loop glucose control with faster insulin aspart compared with standard insulin aspart in adults with type 1 diabetes: A double‐blind, multicentre, multinational, randomized, crossover study

Abstract: Aim: To evaluate the use of hybrid closed‐loop glucose control with faster‐acting insulin aspart (Fiasp) in adults with type 1 diabetes (T1D). Research Design and Methods: In a double‐blind, multinational, randomized, crossover study, 25 adults with T1D using insulin pump therapy (mean ± SD, age 38 ± 9 years, HbA1c 7.4% ± 0.8% [57 ± 8 mmol/mol]) underwent two 8‐week periods of unrestricted living comparing hybrid closed‐loop with Fiasp and hybrid closed‐loop with standard insulin aspart in random order. During both interventions the CamAPS FX closed‐loop system incorporating the Cambridge model predictive control algorithm was used. Results: In an intention‐to‐treat analysis, the proportion of time sensor glucose was in the target range (3.9–10.0 mmol/L; primary endpoint) was not different between interventions (75% ± 8% vs. 75% ± 8% for hybrid closed‐loop with Fiasp vs. hybrid closed‐loop with standard insulin aspart; mean‐adjusted difference −0.6% [95% CI −1.8% to 0.7%]; p < .001 for non‐inferiority [non‐inferiority margin 5%]). The proportion of time with sensor glucose less than 3.9 mmol/L (median [IQR] 2.4% [1.2%–3.2%] vs. 2.9% [1.7%–4.0%]; p = .01) and less than 3.0 mmol/L (median [IQR] 0.4% [0.2%–0.7%] vs. 0.7% [0.2%–0.9%]; p = .03) was reduced with Fiasp versus standard insulin aspart. There was no difference in mean glucose (8.1 ± 0.8 vs. 8.0 ± 0.8 mmol/L; p = .13) or glucose variability (SD of sensor glucose 2.9 ± 0.5 vs. 2.9 ± 0.5 mmol/L; p = .90). Total daily insulin requirements did not differ (49 ± 15 vs. 49 ± 15 units/day; p = .45). No severe hypoglycaemia or ketoacidosis occurred. Conclusions: The use of Fiasp in the CamAPS FX closed‐loop system may reduce hypoglycaemia without compromising glucose control compared with standard insulin aspart in adults with T1D

Consensus Recommendations for the Use of Automated Insulin Delivery (AID) Technologies in Clinical Practice

International audienceThe significant and growing global prevalence of diabetes continues to challenge people with diabetes (PwD), healthcare providers and payers. While maintaining near-normal glucose levels has been shown to prevent or delay the progression of the long-term complications of diabetes, a significant proportion of PwD are not attaining their glycemic goals. During the past six years, we have seen tremendous advances in automated insulin delivery (AID) technologies. Numerous randomized controlled trials and real-world studies have shown that the use of AID systems is safe and effective in helping PwD achieve their long-term glycemic goals while reducing hypoglycemia risk. Thus, AID systems have recently become an integral part of diabetes management. However, recommendations for using AID systems in clinical settings have been lacking. Such guided recommendations are critical for AID success and acceptance. All clinicians working with PwD need to become familiar with the available systems in order to eliminate disparities in diabetes quality of care. This report provides much-needed guidance for clinicians who are interested in utilizing AIDs and presents a comprehensive listing of the evidence payers should consider when determining eligibility criteria for AID insurance coverage

Synthèse et repliement des protéines dans les chloroplastes: effets collatéraux de l'expression massive d'un transgène

Plastid genome engineering is an emerging technology which is being considered for the improvement of plant agronomic traits as well as for the molecular farming of biomaterials and therapeutic proteins. In the first part of this work, the potential of these organelles of prokaryotic origin to correctly fold and accumulate a disulfide bond containing enzyme has been investigated. Unlike a normal bacterial cytosol, the stroma of tobacco chloroplasts was found to support the formation of a recombinant alkaline phosphatase from Escherichia coli, whose activity and stability depend on the presence of two intra-molecular disulfide bonds. Targeting this enzyme to the thylakoid lumen via the Sec pathway resulted in stronger accumulation levels and higher specific activity. Complementary approaches have been initiated in tobacco using bacterial chaperones involved in the catalysis of disulfide bond formation, and a redox sensitive green fluorescent protein. These findings shed some light on the folding properties within chloroplasts, and have important biotechnological implications for the production in plants of many therapeutic proteins. Recombinant chloroplasts have the capacity to accumulate massive amounts of recombinant protein. The second part of this work focused on the consequences on the plant fitness and physiology of such extreme expression levels. We have analyzed tobacco plastid transformants accumulating alkaline phosphatase, a green fluorescent protein, and a bacterial hydroxyphenyl pyruvate dioxygenase. These lines exhibited a normal wild-type growth rate, and no significant perturbation of the chloroplast transcriptome was observed. In contrast, a proteomic approach on leaves revealed some differences, in particular a massive drop in the amount of Rubisco. The impact of recombinant protein expression on plant metabolism is discussed