For many potato cultivars, tuber yield is optimal at average daytime temperatures in the range 14–22 °C. Above this range, tuber yield is reduced for most cultivars. We previously reported that moderately elevated temperature increases steady-state expression of the core circadian clock gene TIMING OF CAB EXPRESSION 1 (StTOC1) in developing tubers, whereas expression of the StSP6A tuberization signal is reduced, along with tuber yield. In this study we provide evidence that StTOC1 links environmental signalling with potato tuberization by suppressing StSP6A autoactivation in the stolons. We show that transgenic lines silenced in StTOC1 expression exhibit enhanced StSP6A transcript levels and changes in gene expression in developing tubers that are indicative of an elevated sink strength. Nodal cuttings of StTOC1 antisense lines displayed increased tuber yields at moderately elevated temperatures, whereas tuber yield and StSP6A expression were reduced in StTOC1 overexpressor lines. Here we identify a number of StTOC1 binding partners and demonstrate that suppression of StSP6A expression is independent of StTOC1 complex formation with the potato homolog StPIF3. Down-regulation of StTOC1 thus provides a strategy to mitigate the effects of elevated temperature on tuber yield.

Guava (Psidium guajavaL.), a major fruit crop of the sub-tropical region, is facing a production decline due to drought stress. Morphophysiological responses to drought stress and underlying transcriptional regulations in guava are, largely, unknown. This study evaluated the drought stress tolerance of two guava cultivars,viz. “Gola” and “Surahi,” at morphological and physiological levels regulated differentially by ESTs (Expressed Sequence Tags). The treatments comprises three moisture regimes,viz. T_o= 100% (control), T₁= 75%, and T₂= 50% of field capacity. There was an overall decrease in both morphological and physiological attributes of studied guava cultivars in response to drought stress. Nonetheless, the water use efficiency of the “Surahi” cultivar increased (41.86%) speculating its higher drought tolerance based on enhanced peroxidase (402%) and catalase (170.21%) activities under 50% field capacity (T₂). Moreover, higher proline and flavonoid contents reinforced drought stress retaliation of the “Surahi” cultivar. The differential expression of a significant number of ESTs in “Surahi” (234) as compared to “Gola” (117) cultivar, somehow, regulated its cellular, biological, and molecular functions to strengthen morphophysiological attributes against drought stress as indicated by the upregulation of ESTs related to peroxidase, sucrose synthase (SUS), alcohol dehydrogenase (ADH), and ubiquitin at morphological, biochemical, and physiological levels. In conclusion, the drought stress acclimation of pear-shaped guava cultivar “Surahi” is due to the increased activities of peroxidase (POD) and catalase (CAT) complimented by the upregulation of related ESTs.

Background: The ASPIRE and ENDEAVOUR trials have shown cardiovascular adverse effects in patients treated with carfilzomib-based regimens. Therefore, we conducted this meta- analysis of published clinical trials to identify the cumulative incidence and risk of cardiovascular adverse effects due to carfilzomib. Methods: A systematic search of PubMed, Embase, Web of Science, and Cochrane library was performed, and we identified 45 prospective trials of carfilzomib with data on 5583 patients. Among all patients being treated with carfilzomib (N=5,583), 8.9% sustained all grade cardiotoxicity, while 4.4% sustained high-grade cardiotoxicity. All-grade hypertension was present in 13.2%, while the incidence of high-grade hypertension was 5.3%. Result: The observed incidences of all-grade heart failure, edema, and ischemia were 5.1%, 20.7%, and 4.6%, respectively. Likewise, for high-grade heart failure and edema observed incidence was 3.2%, and 2.7%, respectively. There was no difference in the event rate of all and highgrade cardiotoxicity between newly diagnosed multiple myeloma and relapsed/refractory (p-value 0.42 and 0.86, respectively). Likewise, we did not observe any difference in the event rate of all and high-grade cardiotoxicity when carfilzomib was used as a single agent versus when used in combination therapy with other agents (p-value 0.43 and 0.73, respectively). Conclusion: Carfilzomib is associated with a significant risk of cardiovascular toxicity and hypertension. With the increasing utilization of carfilzomib, it is critical for primary care physicians, oncologists and cardiologists to be aware of the risk of cardiotoxicity associated with the use of carfilzomib to recognize and treat baseline cardiovascular risk factors in such patients.

Grapefruit is considered as a minor citrus crop in Pakistan and its annual production is less than 0.5% of total citrus production. Grapefruit industry is depending upon pink flesh cultivar ‘Shamber’ and need varietal diversification. Mutation breeding has played a pivotal role in grapefruit crop improvement and most of the commercial cultivars are bud sports or induced mutants which were selected and later released as new cultivars. Flesh color enhancement, seedlessness and low furanocoumarin level have been main objectives for grapefruit breeders. An overview of potential of mutation breeding in grapefruit and leading mutants produced is presented in the following sections. Though physical mutagens have been more successful, breeders’ interest is rising in more precise and targeted mutagenesis technologies including CRISPR/Cas9 which has enormous potential in genome editing and could shorten breeding and selection cycle. The available leading grapefruit cultivars were screened for horticultural traits and potential candidate varieties has been selected for diversification and selection of better parents for breeding programs. Several putative mutants have been developed using gamma irradiated plant material. The effect of irradiation on plant growth, morphology and biochemical properties has been evaluated and salient findings are discussed. The developed genetically diverse material could be useful for future biotechnology applications.