Serine hydroxymethyltransferase6 is involved in growth and resistance against pathogens via ethylene and lignin production in Arabidopsis.

Photorespiratory serine hydroxymethyltransferases (SHMTs) are important enzymes of cellular one-carbon metabolism. In this study, we investigated the potential role of SHMT6 in Arabidopsis thaliana. We found that SHMT6 is localized in the nucleus and expressed in different tissues during development. Interestingly SHMT6 is inducible in response to avirulent, virulent Pseudomonas syringae and to Fusarium oxysporum infection. Overexpression of SHMT6 leads to larger flowers, siliques, seeds, roots, and consequently an enhanced overall biomass. This enhanced growth was accompanied by increased stomatal conductance and photosynthetic capacity as well as ATP, protein, and chlorophyll levels. By contrast, a shmt6 knockout mutant displayed reduced growth. When challenged with Pseudomonas syringae pv tomato (Pst) DC3000 expressing AvrRpm1, SHMT6 overexpression lines displayed a clear hypersensitive response which was characterized by enhanced electrolyte leakage and reduced bacterial growth. In response to virulent Pst DC3000, the shmt6 mutant developed severe disease symptoms and becomes very susceptible, whereas SHMT6 overexpression lines showed enhanced resistance with increased expression of defense pathway associated genes. In response to Fusarium oxysporum, overexpression lines showed a reduction in symptoms. Moreover, SHMT6 overexpression lead to enhanced production of ethylene and lignin, which are important components of the defense response. Collectively, our data revealed that SHMT6 plays an important role in development and defense against pathogens.

Differences in Cardiac Mechanics among Genetically At-Risk First-Degree Relatives: The DCM Precision Medicine Study.

Aims: Among genetically at-risk first-degree relatives (FDRs) of probands with dilated cardiomyopathy (DCM), the ability to detect changes in left ventricular (LV) mechanics with normal LV size and ejection fraction (LVEF) remains incompletely explored. We sought to define a pre-DCM phenotype among at-risk FDRs, including those with variants of uncertain significance (VUSs), using echocardiographic measures of cardiac mechanics. Methods and Results: LV structure and function, including speckle-tracking analysis for LV global longitudinal strain (GLS), were evaluated in 124 FDRs (65% female; median age 44.9 [IQR: 30.6-60.3] years) of 66 DCM probands of European ancestry sequenced for rare variants in 35 DCM genes. FDRs had normal LV size and LVEF. Negative FDRs of probands with pathogenic or likely pathogenic (P/LP) variants (n=28) were a reference group to which negative FDRs of probands without P/LP variants (n=30), FDRs with only VUSs (n=27), and FDRs with P/LP variants (n=39) were compared. In an analysis accounting for age-dependent penetrance, FDRs below the median age showed minimal differences in LV GLS across groups while those above it with P/LP variants or VUSs had lower absolute values than the reference group (-3.9 [95% CI: -5.7, -2.1] or -3.1 [-4.8, -1.4] %-units) and negative FDRs of probands without P/LP variants (-2.6 [-4.0, -1.2] or -1.8 [-3.1, -0.6]). Conclusions: Older FDRs with normal LV size and LVEF who harbored P/LP variants or VUSs had lower absolute LV GLS values, indicating that some DCM-related VUSs are clinically relevant. LV GLS may have utility for defining a pre-DCM phenotype. Clinical Trial Registration: clinicaltrials.gov, NCT03037632.

Exercise interventions for advanced cancer palliative care patients: A systematic literature review and descriptive evidence synthesis of randomized controlled trials.

BACKGROUND: Exercise is often recommended for cancer patients. However, for advanced cancer palliative care patients, it is unclear whether exercise, as a lifestyle intervention, is beneficial for palliative outcomes. AIM: To examine randomized controlled trials assessing the effectiveness of lifestyle exercise interventions on palliative outcomes in patients with advanced stage cancer. DESIGN: Systematic review and descriptive evidence synthesis. DATA SOURCES: Pubmed/Medline, Embase, CINAHL, PsychInfo, and Web of Science were systematically searched from inception to 2022. Two reviewers identified articles and removed duplicates. Next two reviewers independently screened titles and abstracts and then assessed full-texts articles for eligibility. Finally, all six reviewers examined full-text articles for eligibility and conducted the evidence synthesis. RESULTS: Eight randomized controlled trials were included. Studies were heterogeneous making direct comparisons challenging, but were grouped along three categories: aerobic, resistance, or resistance-aerobic exercises. One of three aerobic studies had positive quality-of-life outcomes. Fatigue improved in one aerobic and one combination resistance-aerobic study. Most resistance-aerobic studies and one aerobic study showed improved physical function. All resistance studies showed improvement in at least one outcome. Across all studies, ill health was the most common reason for participant dropout. The most commonly used assessment tools were: Functional Assessment of Cancer Therapy: Fatigue, European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30, and accelerometer. CONCLUSION: Current randomized controlled trials regarding effects of exercise interventions on palliative outcomes for advanced cancer patients show great variability. While studies show promise, no generalizable conclusions can be made. Further research is needed.