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• Noncoding variants of SHOX have a similar clinical impact as coding variants. • CNVs of the regulatory elements are more frequently downstream of the SHOX gene. • Duplications of SHOX s′ downstream are more frequent than deletions. • Intronic variants may cause de novo CNV of SHOX. The short stature homeobox-containing (SHOX) is the most frequently analysed gene in patients classified as short stature patients (ISS) or diagnosed with Leri-Weill dyschondrosteosis (LWD), Langer mesomelic dysplasia (LMD), or Madelung deformity (MD). However, clinical testing of this gene focuses primarily on single nucleotide variants (SNV) in its coding sequences and copy number variants (CNV) overlapping SHOX gene. This review summarizes the clinical impact of variants in noncoding regions of SHOX. CNV extending exclusively into the regulatory elements (i.e., not interrupting the coding sequence) are found more frequently in downstream regulatory elements of SHOX. Further, duplications are more frequent than deletions. Interestingly, downstream duplications are more common than deletions in patients with ISS or LWD but no such differences exist for upstream CNV. Moreover, the presence of specific CNVs in the patient population suggests the involvement of additional unknown factors. Some of its intronic variants, notably NM_000451.3(SHOX):c.-9delG and c.-65C>A in the 5′UTR, have unclear clinical roles. However, these intronic SNV may increase the probability that other CNV will arise de novo in the SHOX gene based on homologous recombination or incorrect splicing of mRNA. This review highlights the clinical impact of noncoding changes in the SHOX gene and the need to apply new technologies and genotype-phenotype correlation in their analysis. [ABSTRACT FROM AUTHOR]

Cytokinins are plant hormones with biological functions ranging from coordination of plant growth and development to the regulation of senescence. A series of 2-chloro- N 6 -(halogenobenzylamino)purine ribosides was prepared and tested for cytokinin activity in detached wheat leaf senescence, tobacco callus and Amaranthus bioassays. The synthetic compounds showed significant activity, especially in delaying senescence in detached wheat leaves. They were also tested in bacterial receptor bioassays using both monocot and dicot members of the cytokinin receptor family. Most of the derivatives did not trigger cytokinin signaling via the AHK3 and AHK4 receptors from Arabidopsis thaliana in the bacterial assay, but some of them specifically activated the ZmHK1 receptor from Zea mays and were also more active than the aromatic cytokinin BAP in an ARR5::GUS cytokinin bioassay using transgenic Arabidopsis plants. Whole transcript expression analysis was performed using an Arabidopsis model to gather information about the reprogramming of gene transcription when senescent leaves were treated with selected C2-substituted aromatic cytokinin ribosides. Genome-wide expression profiling revealed that the synthetic halogenated derivatives induced the expression of genes related to cytokinin signaling and metabolism. They also prompted both up- and down-regulation of a unique combination of genes coding for components of the photosystem II (PSII) reaction center, light-harvesting complex II (LHCII), and the oxygen-evolving complex, as well as several stress factors responsible for regulating photosynthesis and chlorophyll degradation. Chlorophyll content and fluorescence analyses demonstrated that treatment with the halogenated derivatives increased the efficiency of PSII photochemistry and the abundance of LHCII relative to DMSO- and BAP-treated controls. These findings demonstrate that it is possible to manipulate and fine-tune leaf longevity using synthetic aromatic cytokinin analogs. [ABSTRACT FROM AUTHOR]

The optimal surgical strategy for treating internal carotid artery (ICA) blood blister-like aneurysms (BBAs) has remained unclear. Although some have preferred bypass surgery, others have favored less-demanding surgical methods. The aim of the present meta-analysis was to assess the efficacy, safety, and outcomes of bypass and non–bypass surgical methods when intended as primary treatment of ICA BBAs. Studies reporting data on the outcomes of interest for surgically treated patients with ICA BBAs were searched for in the PubMed/MEDLINE, Evidence-Based Medicine Reviews, Cochrane Central, ProQuest, and Scopus databases. The data were analyzed using random effects modeling. Seven observational studies involving 140 patients met the inclusion criteria. The patients treated with bypass surgery, compared with those treated with non–bypass techniques, had lower odds of poor outcomes (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.28–2.02; P = 0.57; I 2 = 0%), postoperative vasospasm (OR, 1.73; 95% CI, 0.38–7.92; P = 0.48; I 2 = 19%), intraoperative bleeding (OR, 3.37; 95% CI, 0.82–13.90; P = 0.09; I 2 = 0%), postoperative bleeding (OR, 1.91; 95% CI, 0.47–7.76; P = 0.36; I 2 = 0%), and postoperative recurrence of BBAs (OR, 2.16; 95% CI, 0.54–8.66; P < 0.28; I 2 = 0%). No comparison, however, achieved statistical significance. For surgeons who use both bypass and non–bypass surgical strategies, the 2 methods seemed comparable in terms of the outcomes of interest, although the bypass technique appeared superior. However, comparisons with studies reporting bypass as the uniquely preferred technique have indicated that specialization in, and preference for, the bypass procedure has been associated with more favorable outcomes. [ABSTRACT FROM AUTHOR]