losing spondylitis, juvenile rheumatoid arthritis, plaque psoriasis, and psoriatic arthritis, its use in treating CTL-mediated SCARs has not yet been approved (37). We aimed to evaluate the efficacy and safety of etanercept for CTL-mediated SCARs treatment in this randomized trial and further investigate the therapeutic mechanism of etanercept in CTL-mediated SCARs.

Phytochrome photoreceptors enable plants to perceive divergent light signals leading to adaptive changes in response to differing environmental conditions. However, the mechanism of light signal transduction is not fully understood. Here we report the identification of a new signaling intermediate from Arabidopsis thaliana, Scarecrow-like (SCL)13, which serves as a positive regulator of continuous red light signals downstream of phytochrome B (phyB). SCL13 antisense lines exhibit reduced sensitivity towards red light, but only a distinct subset of phyB-mediated responses is affected, indicating that SCL13 executes its major role in hypocotyl elongation during de-etiolation. Genetic evidence suggests that SCL13 is also needed to modulate phytochrome A (phyA) signal transduction in a phyB-independent way. The SCL13 protein is localized in the cytoplasm, but can also be detected in the nucleus. Overexpression of both a nuclear and cytoplasmic localized SCL13 protein leads to a hypersensitive phenotype under red light indicating that SCL13 is biologically active in both compartments. SCL13 is a member of the plant-specific GRAS protein family, which is involved in various different developmental and signaling pathways. A previously identified phytochrome A signaling intermediate, PAT1, belongs to the same subbranch of GRAS proteins as SCL13. Although both proteins are involved in phytochrome signaling, each is specific for a different light condition and regulates a different subset of responses.

Circadian rhythms of gene expression are generated by the combinatorial action of transcriptional and translational feedback loops as well as chromatin remodelling events. Recently, long noncoding RNAs (lncRNAs) that are natural antisense transcripts (NATs) to transcripts encoding central oscillator components were proposed as modulators of core clock function in mammals (Per) and fungi (frq/qrf). Although oscillating lncRNAs exist in plants, their functional characterization is at an initial stage. By screening an Arabidopsis thaliana lncRNA custom-made array we identified CDF5 LONG NONCODING RNA (FLORE), a circadian-regulated lncRNA that is a NAT of CDF5. Quantitative real-time RT-PCR confirmed the circadian regulation of FLORE, whereas GUS-staining and flowering time evaluation were used to determine its biological function. FLORE and CDF5 antiphasic expression reflects mutual inhibition in a similar way to frq/qrf. Moreover, whereas the CDF5 protein delays flowering by directly repressing FT transcription, FLORE promotes it by repressing several CDFs (CDF1, CDF3, CDF5) and increasing FT transcript levels, indicating both cis and trans function. We propose that the CDF5/FLORE NAT pair constitutes an additional circadian regulatory module with conserved (mutual inhibition) and unique (function in trans) features, able to fine-tune its own circadian oscillation, and consequently, adjust the onset of flowering to favourable environmental conditions.

BackgroundThe aim of this study was to evaluate the changes in the cognitive performance of migraine patients using a comprehensive series of cognitive/behavioral and electrophysiological tests.MethodA randomized, cross-sectional, within subject approach was used to compare neuropsychological and electrophysiological evaluations from migrane-affected and healthy subjects.ResultsThirty-four patients with migraine (6 males, 28 females, average 36 years old) were included. Migraineurs performed worse in the majority of the Montreal Cognitive Assessment (MoCA) (p = 0.007) compared to the healthy subjects, significantly in language (p = 0.005), memory (p = 0.006), executive functions (p = 0.042), calculation (p = 0.018) and orientation (p = 0.012). Migraineurs had a lower score on the memory trial of the Rey–Osterrieth complex figure test (ROCF) (p = 0.012). The P3 latency in Fz, Cz, Pz was prolonged in migraineurs compared with the normal control group (P < 0.001). In addition, we analyzed significant correlations between MoCA score and the duration of migraine. We also observed that a decrease in the MoCA-executive functions and calculation score and in the ROCF-recall score were both correlated to the frequency of migraine. Migraineurs were more anxious than healthy subjects (p = 0.001), which is independent of cognitive testing. Differences were unrelated to age, gender and literacy.ConclusionsCognitive performance decreases during migraine, and cognitive dysfunction can be related to the duration and frequency of a migraine attack.

BackgroundTuberculosis is a serious global health problem. Its paradigms are shifting through time, especially in rapidly developing countries such as China. Health providers in China are at the forefront of the battle against tuberculosis; however, there are few empirical studies on health providers' perspectives on the challenges they face in tuberculosis control at the county level in China. This study was conducted among health providers to explore their experiences with tuberculosis control in order to identify bottlenecks and emerging challenges in controlling tuberculosis in rural China.MethodsA qualitative approach was used. Semi-structured, in-depth interviews were conducted with 17 health providers working in various positions within the health system of one rural county (ZJG) of China. Data were analyzed based on thematic content analysis using MAXQDA 10 qualitative data analysis software.ResultsHealth providers reported several problems in tuberculosis control in ZJG county. Migrant workers and the elderly were repeatedly documented as the main obstacles in effective tuberculosis control in the county. At a personal level, doctors showed their frustration with the lack of new drugs for treating tuberculosis patients, and their opinions varied regarding incentives for referring patients.ConclusionThe results suggest that several problems still remain for controlling tuberculosis in rural China. Tuberculosis control efforts need to make reaching the most vulnerable populations a priority and encourage local health providers to adopt innovative practices in the local context based on national guidelines to achieve the best results. Considerable changes in China's National Tuberculosis Control Program are needed to tackle these emerging challenges faced by health workers at the county level.

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Drought is a major environmental factor that limits plant growth and crop productivity. Genetic engineering is an effective approach to improve drought tolerance in various crops, including rice (Oryza sativa). Functional characterization of relevant genes is a prerequisite when identifying candidates for such improvements. We investigated OsSGL (Oryza sativa Stress tolerance and Grain Length), a novel DUF1645 domain-containing protein from rice. OsSGL was up-regulated by multiple stresses and localized to the nucleus. Transgenic plants over-expressing or hetero-expressing OsSGL conferred significantly improved drought tolerance in transgenic rice and Arabidopsis thaliana, respectively. The overexpressing plants accumulated higher levels of proline and soluble sugars but lower malondialdehyde (MDA) contents under osmotic stress. Our RNA-sequencing data demonstrated that several stress-responsive genes were significantly altered in transgenic rice plants. We unexpectedly observed that those overexpressing rice plants also had extensive root systems, perhaps due to the altered transcript levels of auxin- and cytokinin-associated genes. These results suggest that the mechanism by which OsSGL confers enhanced drought tolerance is due to the modulated expression of stress-responsive genes, higher accumulations of osmolytes, and enlarged root systems.

Phytochrome A (phyA) is the photolabile plant light receptor that mediates broad spectrum very low-fluence responses and high irradiance responses to continuous far-red light (FR c ). An Arabidopsis mutant laf3-1 (long after far-red 3) was recovered from a screen for transposon-tagged mutants that exhibit reduced inhibition of hypocotyl elongation in FR c . The laf phenotype correlated well with a strongly attenuated disappearance of XTR7 transcript in FR c . The effects of laf3-1 on phyA-controlled CAB, CHS, and PET H expression were more subtle, and the mutation had no clear effects on PET E and ASN1 transcript levels in FR c . The use of two alternative transcription initiation sites in the LAF3 gene generates two isoforms that differ only at their N termini. Transcripts encoding both isoforms were induced during germination and were present at slightly higher levels in de-etiolated seedlings than in those grown in darkness. No significant differential regulation of the two isoforms was observed upon exposure to either FR c or continuous red light. Transcripts encoding the shorter isoform (LAF3 ISF2 ) always appear to be more abundant than those encoding the longer isoform (LAF3 ISF1 ). However, both isoforms were capable of full complementation of the laf3-1 hypocotyl phenotype in FR c . When fused to a yellow fluorescent protein, both isoforms localize to the perinuclear region, suggesting that LAF3 encodes a product that might regulate nucleo-cytoplasmic trafficking of an intermediate(s) involved in phyA signal transduction.Phytochromes are soluble chromoproteins that regulate plant growth and development by their ability to interconvert between two stable spectral forms. Red light (R) converts the R-absorbing Pr form (the form synthesized in darkness) to the Pfr (far-red absorbing form) and far-red light (FR) reconverts Pfr to Pr. Two important features distinguish phytochrome A (phyA) from the other four phytochromes in Arabidopsis. First, although the Arabidopsis phytochromes phyB to phyE are activated exclusively by R and inactivated by irradiation with FR, phyA can be activated by FR and low fluences of R and blue light (B). Secondly, although phyA levels decrease rapidly after exposure to light as a result of both down-regulation of PHYA gene transcription (Cantó n and Quail, 1999) and far greater photolability of phyA than other phytochromes (Sharrock and Clack, 2002), phyA is by far the most abundant phytochrome in etiolated seedlings. These features enable phyA to perform a seminal role in triggering the shift between skotomorphogenesis and photomorphogenesis. Together, they ensure that the inhibition of hypocotyl elongation, and the activation of physiological changes needed to ensure photosynthetic competence are already underway when seedlings emerge from the soil surface. Despite its lability in light-grown plants, the influence of phyA throughout the life cycle is evidenced by its involvement in sensing photoperiod to ensure that flowering is initiated at the proper time (Johnson et al., 199...