Warm temperature promotes flowering in Arabidopsis thaliana and this response involves multiple signalling pathways. To understand the temporal dynamics of temperature perception, tests were carried out to determine if there was a daily window of enhanced sensitivity to warm temperature (28 °C). Warm temperature applied during daytime, night-time, or continuously elicited earlier flowering, but the effects of each treatment were unequal. Plants exposed to warm night (WN) conditions flowered nearly as early as those in constant warm (CW) conditions, while treatment with warm days (WD) caused later flowering than either WN or CW. Flowering in each condition relied to varying degrees on the activity of CO , FT , PIF4 , and PIF5 , as well as the action of unknown genes. The combination of signalling pathways involved in flowering depended on the time of the temperature cue. WN treatments caused a significant advance in the rhythmic expression waveform of CO, which correlated with pronounced up-regulation of FT expression, while WD caused limited changes in CO expression and no stimulation of FT expression. WN- and WD-induced flowering was partially CO independent and, unexpectedly, dependent on PIF4 and PIF5 . pif4-2, pif5-3, and pif4-2 pif5-3 mutants had delayed flowering under all three warm conditions. The double mutant was also late flowering in control conditions. In addition, WN conditions alone imposed selective changes to PIF4 and PIF5 expression. Thus, the PIF4 and PIF5 transcription factors promote flowering by at least two means: inducing FT expression in WN and acting outside of FT by an unknown mechanism in WD.

tection and vibratory detection thresholds also significantly increased with HFS compared to ON states (p = 0.04 and p = 0.01, respectively). In addition, HFS significantly decreased 10-and 40-gram pinprick detection compared to OFF states (both p = 0.01). No significant differences between OFF, ON and HFS states were seen in thermal and thermal pain detection. Conclusion: HFS is a new means of modulating chronic pain. The mechanism by which HFS works seems to differ from that of traditional SCS, offering a new platform for innovative advancements in treatment and a greater potential to treat patients by customizing waveforms.

Introduction: High-frequency spinal cord stimulation (HFSCS) offers an alternative treatment for chronic refractory pain syndromes nonresponsive to traditional spinal cord stimulation (SCS). Following the conflicting findings of preliminary HFSCS clinical studies performed at 5-10 kHz, this study is the first to report successful clinical usage of 1-kHz frequency SCS with a standard generator. Patients: We used HFSCS in 2 patients who had inadequate relief with traditional SCS. Patient 1 was initially programmed at 40 Hz and a pulse width of 330 μs with bipolar stimulation. After multiple setting adjustments with inadequate pain relief, the patient was reprogrammed to HFSCS at settings of 1.15 kHz, 120 μs, and 5 V. Patient 2 was initially programmed at a frequency of 1.2 kHz and a pulse width of 120 μs, which she favored over the standard setting of 40 Hz and 390 μs pulse width. HFSCS provided optimal pain alleviation and increased quality of life for both patients. Conclusions: HFSCS at the frequency of 1 kHz offers a new tool for treatment of chronic pain in patients with traditional stimulation settings. Furthermore, most standard SCS batteries are capable of delivering stimulation in this frequency range.

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