hi2-1, A QTL which improves harvest index, earliness and alters metabolite accumulation of processing tomatoes

Harvest index, defined as the ratio of reproductive yield to total plant biomass, and early ripening are traits with important agronomic value in processing tomatoes. The Solanum pennellii introgression-line (IL) population shows variation for harvest index and earliness. Most of the QTL mapped for these traits display negative agronomic effects; however, hi2-1 is a unique QTL displaying improved harvest index and earliness. This introgression was tested over several years and under different genetic backgrounds. Thirty-one nearly isogenic sub-lines segregating for the 18 cM TG33–TG276 interval were used for fine mapping of this multi-phenotypic QTL. Based on this analysis the phenotypic effects for plant weight, Brix, total yield and earliness were co-mapped to the same region. In a different mapping experiment these sub-lines were tested as heterozygotes in order to map the harvest index QTL which were only expressed in the heterozygous state. These QTL mapped to the same candidate region, suggesting that hi2-1 is either a single gene with pleiotropic effects or represents linked genes independently affecting these traits. Metabolite profiling of the fruit pericarp revealed that a number of metabolic QTL co-segregate with the harvest index trait including those for important transport assimilates such as sugars and amino acids. Analysis of the flowering pattern of these lines revealed induced flowering at IL2-1 plants, suggest that hi2-1 may also affect harvest index and early ripening by changing plant architecture and flowering rate

SAFETY OF BRONCHOALVEOLAR LAVAGE IN HEMATOLOGICAL PATIENTS WITH THROMBOCYTOPENIA – A RETROSPECTIVE COHORT STUDY

Background Hospitalized hematological patients often require bronchoalveolar lavage (BAL). Paucity of evidence exists as to the potential risks in patients with very-severe thrombocytopenia (VST). Methods This retrospective-cohort study included adult hematological in-patients with VST, defined as platelets<20x103/μL, undergoing BAL during 2012-2021. Mechanically-ventilated patients or those with known active bleeding were excluded. Primary outcomes included major bleeding halting the BAL or deemed significant by the treating physician, need for any respiratory support other than low flow O2 or death within 24 hours. Any other bleeding were recorded as secondary outcomes.    Results Of the 507 patients included in the final analysis, the 281 patients with VST had lower hemoglobin (Md=0.3, p=0.003), longer prothrombin-time (Md=0.7s, p=0.025), higher chances of preprocedural platelet transfusion (RR 3.68, 95%CI[2.86,4.73]), and only one primary-outcome event (death of septic shock 21h postprocedurally) - compared with 3 (1.3%) events (two bleedings halting procedure and one need for non-invasive-ventilation) in patients with platelets ≥20x103/μL (p=0.219). Risk of minor, spontaneously resolved bleeding was higher (RR=3.217, 95%CI[0.919,11.262]) in patients with VST (4.3% vs 1.3%, p=0.051). No association was found between any of the complications recorded and preprocedural platelets, age, aPTT, PT, hematological status, or platelet transfusion.  Conclusions This data suggests BAL to be safe even when platelet counts are <20x103/μL

Beta-2-transferrin to detect cerebrospinal fluid pleural effusion: a case report

Abstract Introduction Pleural effusion secondary to ventriculoperitoneal shunt insertion is a rare and potentially life-threatening occurrence. Case presentation We describe a 14-month-old Caucasian boy who had a ventriculoperitoneal shunt inserted for progressive hydrocephalus of unknown etiology. Two and a half months post-shunt insertion, the patient presented with mild respiratory distress. A chest radiograph revealed a large right pleural effusion and a shunt series demonstrated an appropriately placed distal catheter tip. A subsequent abdominal ultrasound revealed marked ascites. Fluid drained via tube thoracostomy was sent for beta-2-transferrin electrophoresis. A positive test was highly suggestive of cerebral spinal fluid hydrothorax. Post-externalization of the ventriculoperitoneal shunt, the ascites and pleural effusion resolved. Conclusion Testing for beta-2-transferrin protein in pleural fluid may serve as a useful technique for diagnosing cerebrospinal fluid hydrothorax in patients with ventriculoperitoneal shunts

Degrons in Protein Substrates Program the Speed and Operating Efficiency of the AAA+ Lon Proteolytic Machine

AAA+ proteases are ATP-fueled machines that bind protein substrates via a degradation tag, unfold the molecule if necessary, and then translocate the polypeptide into a chamber for proteolysis. Tag recognition is normally viewed as a passive reaction. By contrast, for the AAA+ Lon protease, we show that degron tags are also regulatory elements that determine protease activity levels. Indeed, different tags fused to the same protein change degradation speeds and energetic efficiencies by 10-fold or more. Degron binding to multiple sites in the Lon hexamer appears to differentially stabilize specific enzyme conformations, including one with high protease and low ATPase activity, and results in positively cooperative degradation. These allosteric mechanisms allow Lon to operate in either a fast or slow proteolysis mode, according to specific physiological needs, and may help maximize degradation of misfolded proteins following stress-induced denaturation.National Institutes of Health (U.S.) (Grant AI-15706 and AI-16892

Recognition of misfolded proteins by Lon, a AAA+ protease

Proteins unfold constantly in cells, especially under stress conditions. Degradation of denatured polypeptides by Lon and related ATP-dependent AAA+ proteases helps prevent toxic aggregates formation and other deleterious consequences, but how these destructive enzymatic machines distinguish between damaged and properly folded proteins is poorly understood. Here, we show that Escherichia coli Lon recognizes specific sequences—rich in aromatic residues—that are accessible in unfolded polypeptides but hidden in most native structures. Denatured polypeptides lacking such sequences are poor substrates. Lon also unfolds and degrades stably folded proteins with accessible recognition tags. Thus, protein architecture and the positioning of appropriate targeting sequences allow Lon degradation to be dependent or independent of the folding status of a protein. Our results suggest that Lon can recognize multiple signals in unfolded polypeptides synergistically, resulting in nanomolar binding and a mechanism for discriminating irreversibly damaged proteins from transiently unfolded elements of structure