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A wide range of processes in plants, including expression of certain genes, is regulated by endogenous circadian rhythms. The circadian clock-associated 1 (CCA1) and the late elongated hypocotyl (LHY) proteins have been shown to be closely associated with clock function in Arabidopsis thaliana. The protein kinase CK2 can interact with and phosphorylate CCA1, but its role in the regulation of the circadian clock remains unknown. Here we show that plants overexpressing CKB3, a regulatory subunit of CK2, display increased CK2 activity and shorter periods of rhythmic expression of CCA1 and LHY. CK2 is also able to interact with and phosphorylate LHY in vitro. Additionally, overexpression of CKB3 shortened the periods of four known circadian clock-controlled genes with different phase angles, demonstrating that many clock outputs are affected. This overexpression also reduced phytochrome induction of an Lhcb gene. Finally, we found that the photoperiodic flowering response, which is influenced by circadian rhythms, was diminished in the transgenic lines, and that the plants flowered earlier on both long-day and short-day photoperiods. These data demonstrate that CK2 is involved in regulation of the circadian clock in Arabidopsis.

We have isolated the gene for a protein designated CCA1. This protein can bind to a region of the promoter of an Arabidopsis light-harvesting chlorophyll a/b protein gene, Lhcb1*3, which is necessary for its regulation by phytochrome. The CCA1 protein interacted with two imperfect repeats in the Lhcb1*3 promoter, AA(A/C)AATCT, a sequence that is conserved in Lhcb genes. A region near the N terminus of CCA1, which has some homology to the repeated sequence found in the DNA binding domain of Myb proteins, is required for binding to the Lhcb1*3 promoter. Lines of transgenic Arabidopsis plants expressing antisense RNA for CCA1 showed reduced phytochrome induction of the endogenous Lhcb1*3 gene, whereas expression of another phytochrome-regulated gene, rbcS-1A, which encodes the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase, was not affected. Thus, the CCA1 protein acts as a specific activator of Lhcb1*3 transcription in response to brief red illumination. The expression of CCA1 RNA was itself transiently increased when etiolated seedlings were transferred to light. We conclude that the CCA1 protein is a key element in the functioning of the phytochrome signal transduction pathway leading to increased transcription of this Lhcb gene in Arabidopsis

Purpose This study aims to investigate the moderating role of low and high failure severity levels on recovery satisfaction and on behavioral intentions through recovery satisfaction. This research adopted justice theory and regulatory focus theory to provide further explanations on the inconsistencies in the extant literature regarding service failure and responses to service recovery. Design/methodology/approach This study applied a scenario-based experimental design of two (perceived justice: low vs high) by two (failure severity: low vs high) between-subjects factorial design. Data was collected from 237 mobile phone users recruited via convenience sampling. This study examined the hypothesized relations using Hayes (2018) PROCESS macro version 4.0. Findings Perceived justice had a higher positive effect on recovery satisfaction at a high failure severity level. The direct effect of perceived justice on behavioral intentions was significant and positive only at a high level of failure severity, whereas the indirect effect of perceived justice on consumers’ positive behavior through recovery satisfaction was more positive at a high level of failure severity. Research limitations/implications Justice theory and regulatory focus theory can be used to explain how a well-implemented recovery effort can offset losses that are caused by a highly severe service failure leading to satisfaction and positive responses. However, as this study was conducted within a telecommunication service context, this research needs to be replicated in other areas, including the use of other data collection methods and measurement of consumers’ regulatory focus orientation. Practical implications The findings of this study provide managers with valuable insights into the allocation of service providers’ resources for recovery actions according to consumers’ perceived severity levels to regain consumer satisfaction and continued positive behavioral intentions. Originality/value Past research on the effect of failure severity levels on recovery satisfaction and consumers’ positive behavioral intentions is scant, and those studies that examined severity levels have shown conflicting results. This study attempted to advance the research by examining the relationship between perceived justice, recovery satisfaction and behavioral intentions at low and high failure severity levels using justice theory and regulatory focus theory. None of the theories have been examined concurrently in the service failure and recovery framework.

Type 2 diabetes risk is associated with low birth weight, rapid weight gain during childhood, and shorter stature and lower circulating IGF-I levels in adults. The largest variations in growth rates occur during the first postnatal years. We hypothesised that early postnatal variations in height and weight gain and IGF-I levels may be associated with risk markers for adult disease. We measured the fasting insulin sensitivity (Homeostasis model) and insulin secretion post-oral glucose (insulinogenic index 0-30 min) in 851 normal 8-year-old children from a prospective birth cohort. We examined associations between size at birth, postnatal weight gain and circulating IGF-I levels with insulin sensitivity and secretion at 8 years of age. Fasting insulin sensitivity at 8 years was closely related to current BMI (r= -0.33, p<0.0005). Lower insulin sensitivity and higher BMI and waist circumference were all predicted by greater weight gain between birth to 3 years of age (all p<0.0005); lower birth weight was associated with reduced insulin sensitivity only in the highest current BMI tertile ( r=0.17, p=0.006). In contrast, lower insulin secretion was related to smaller size at birth ( p=0.01), independent of postnatal weight gain and insulin sensitivity. Lower insulin secretion was also independently related to shorter stature at 8 years of age relative to parental height ( p=0.047) and with lower plasma IGF-I levels at 5 years of age ( n=252, p=0.004). Associations between lower birth weight and insulin resistance may be dependent on rapid weight gain during the early postnatal years. However, irrespective of postnatal weight gain, smaller size at birth, lower IGF-I levels and lower childhood height predicted reduced compensatory insulin secretion.

Background The common palm civet ( Paradoxurus musangus ) is a species native to Southeast Asia. Highly adapted to urbanised environments, these civets can often be found in proximity to humans and companion animals, raising the concern of pathogen transmission at the human-wildlife and wildlife-domestic animal interface. Whilst there have been reports of various bacteria and viruses detected in civets, little is known about the protozoa that they may harbour. In this study, we screened the common palm civets in Singapore for tick-borne protozoan parasites known as piroplasms. Methods Over a 2-year period, blood samples were opportunistically collected from 135 wild common palm civets following a physical examination. The sex and weight of each civet were recorded, and any ectoparasites detected were identified through DNA barcoding. DNA extracts of blood samples were screened using a PCR assay targeting the 18S rRNA gene of piroplasmids. Results A novel Cytauxzoon species was detected in 29 civets (21.5%), and a statistically significant association was found between infection and the civet’s weight. Two cat flea ( Ctenocephalides felis ) specimens were discovered on two sampled civets; however, Cytauxzoon DNA was not detected in either the flea or the sampled civet. Phylogenetic analysis of the Cytauxzoon 18S rRNA gene sequences from 29 civets revealed that this piroplasmid is most closely related to a Cytauxzoon sp. detected in meerkats in South Africa but molecularly distinct from the six currently described Cytauxzoon species. Conclusions This detection documents the first molecular confirmation of Cytauxzoon sp. infection in Southeast Asia and the first report of Cytauxzoon sp. in a viverrid host. Further studies are required to determine the vector involved in the transmission of this novel Cytauxzoon species, as no ticks were found on the sampled civets. The discovery of Cytauxzoon paradoxurus n. sp. highlights the importance of expanded biosurveillance to better understand the diversity of piroplasms harboured by wildlife in the region and its potential for cross-species transmission. Graphical Abstract

Background Babesia is a protozoal, tick-borne parasite that can cause life-threatening disease in humans, wildlife and domestic animals worldwide. However, in Southeast Asia, little is known about the prevalence and diversity of Babesia species present in wildlife and the tick vectors responsible for its transmission. Recently, a novel Babesia species was reported in confiscated Sunda pangolins ( Manis javanica ) in Thailand. To investigate the presence of this parasite in Singapore, we conducted a molecular survey of Babesia spp. in free-roaming Sunda pangolins and their main ectoparasite, the Amblyomma javanense tick. Methods Ticks and tissue samples were opportunistically collected from live and dead Sunda pangolins and screened using a PCR assay targeting the 18S rRNA gene of Babesia spp. DNA barcoding of the cytochrome oxidase subunit I ( COI ) mitochondrial gene was used to confirm the species of ticks that were Babesia positive. Results A total of 296 ticks and 40 tissue samples were obtained from 21 Sunda pangolins throughout the 1-year study period. Babesia DNA was detected in five A. javanense ticks (minimum infection rate = 1.7%) and in nine different pangolins (52.9%) located across the country. Phylogenetic analysis revealed that the Babesia 18S sequences obtained from these samples grouped into a single monophyletic clade together with those derived from Sunda pangolins in Thailand and that this evolutionarily distinct species is basal to the Babesia sensu stricto clade, which encompasses a range of Babesia species that infect both domestic and wildlife vertebrate hosts. Conclusions This is the first report documenting the detection of a Babesia species in A. javanense ticks, the main ectoparasite of Sunda pangolins. While our results showed that A. javanense can carry this novel Babesia sp., additional confirmatory studies are required to demonstrate vector competency. Further studies are also necessary to investigate the role of other transmission pathways given the low infection rate of ticks in relation to the high infection rate of Sunda pangolins. Although it appears that this novel Babesia sp. is of little to no pathogenicity to Sunda pangolins, its potential to cause disease in other animals or humans cannot be ruled out. Graphical abstract

OBJECTIVE: To investigate whether circulating levels of fibroblast growth factor 21 (FGF21), which previously has been shown to be elevated in obesity, could predict the development of type 2 diabetes in a 5.4-year, population-based, prospective study. RESEARCH DESIGN AND METHODS: Baseline plasma FGF21 levels were measured using an enzyme-linked immunosorbent assay in 1,900 subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS). The prospective association of FGF21 with diabetes development over 5.4 years was analyzed using multiple logistic regression. RESULTS: At baseline, plasma levels of FGF21 increased progressively with worsening dysglycemia from normal glucose tolerance, through prediabetes, to diabetes (global trend, P < 0.001). Of 1,292 subjects without diabetes at baseline, a high baseline FGF21 level was a strong independent predictor for diabetes development (odds ratio 1.792; P < 0.01), together with waist circumference and fasting plasma glucose levels. CONCLUSIONS: Plasma FGF21 levels were significantly increased in subjects with prediabetes and diabetes and predicted the development of diabetes in humans.

In the present work, Pt/MCNTs and P-dopedPt/MCNTs catalysts were synthesized via hydrothermal method and utilized for glycerol oxidation reaction (GOR). The catalysts were physio-chemically characterized by Brunauer-Emmett-Teller (BET), X-ray diffraction, field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM) to investigate pore size, pore volume, structure and morphology of the catalysts. A remarkable reduction in BET surface area was found for P-dopedPt/MNCTs which 1.56 time less than the sole MNCTs is confirming the incorporation of phosphorous into the pore channels of Pt/MCNT. The TEM analysis of P-dopedPt/MCNTS demonstrated the uniform distribution of Pt nanoparticles over multiwalled carbon nanotubes with an average particle size of 6.23 nm. The activity and stability of the catalysts were analysed for GOR using cyclic voltammetry (CV) and chronoamperometry (CA). The CV testing showed the higher current density for P-doped Pt/MCNTs (28.33 A/m2) which is 2 times higher than the Pt/MCNTs (14.20 A/m2) current density. The synthesized products were analysed by high performance liquid chromatography (HPLC) analysis which demonstrated the selective synthesis of tartronic acid as a major product with maximum yield. It was found that the P-dopedPt/MCNTs have higher selectivity for tartronic acid and glyceric acid as compared to its counterpart.

ObjectiveTreatment efficacy of androgen deprivation therapy with radical prostatectomy for intermediate- to high-risk prostate cancer is less well-studied. The NEAR trial is a single-arm, phase II investigation of neoadjuvant apalutamide monotherapy and radical prostatectomy (RP) in the treatment of D’Amico intermediate- and high-risk prostate cancer (NCT03124433).Materials and methodsPatients with histologically-proven, D’Amico intermediate- to high-risk prostate adenocarcinoma received apalutamide 240 mg once-daily for 12 weeks followed by RP + /−lymphadenectomy. Primary outcome was pathological complete response (pCR) rate. Secondary outcomes included rate of biochemical response (defined by PSA < 0.03 ng/mL at week 24 from starting apalutamide without subsequent PSA relapse), treatment-related adverse events, and RP complication rates. Correlative biomarker analyses were performed to examine for molecular predictors of treatment responses.ResultsFrom 2017 to 2019, 30 patients were recruited, of which 20 and 10 were high and intermediate risk, respectively; 25 completed treatment as per-protocol. We did not observe any pCR on trial; median reduction of cancer burden was 41.7% (IQR: 33.3%–60.0%). 18 out of 25 patients were classified as having a biochemical response (4 did not achieve PSA of <0.03 ng/mL at week 24 and 3 developed PSA relapse subsequently). Dry skin (N = 16; 53.3%), fatigue (N = 10; 33.3%) and skin rash (N = 9; 30.0%) were the most common adverse events, and there was no major peri-operative complication. We observed an association between tumours of low androgen receptor activity and PAM50 basal status with biochemical non-responders, albeit these molecular phenotypes were not associated with pathological response.ConclusionsA 12-week course of neoadjuvant apalutamide prior to RP did not meet the primary endpoint of pCR in this trial. Tumours with low androgen receptor activity or of the PAM50 basal subtype may have a reduced response to apalutamide.

Aims/hypothesis Hypoadiponectinaemia and raised C-reactive protein (CRP) level are obesity-related biomarkers associated with glucose dysregulation. We evaluated the combined use of these two biomarkers in predicting the deterioration of glycaemia in a prospective study after a median of 5.4 years. Methods In total 1,288 non-diabetic participants from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2, with high-sensitivity CRP (hsCRP) and total adiponectin levels measured were included. OGTT was performed in all participants. Two hundred and six participants had deterioration of glycaemia at follow-up, whereas 1,082 participants did not. Results Baseline age, hsCRP and adiponectin levels were significant independent predictors of the deterioration of glycaemia in a Cox regression analysis after adjusting for baseline age, sex, BMI, hypertension, triacylglycerols, 2 h post-OGTT glucose and homeostasis model assessment of insulin resistance index (all p  < 0.01). The introduction of hsCRP or adiponectin level to a regression model including the other biomarker improved the prediction of glycaemic progression significantly in all participants, especially in women (all p  < 0.01). The combined inclusion of the two biomarkers resulted in a modest improvement in model discrimination, compared with the inclusion of either one alone. Among participants with impaired fasting glucose/impaired glucose tolerance (IFG/IGT) at baseline, hsCRP and adiponectin levels were not predictive of progression or improvement of glycaemic status. Conclusions/interpretation Adiponectin and hsCRP levels are independent factors in predicting the deterioration of glycaemia, supporting the role of adiposity-related inflammation in the development of type 2 diabetes. Their combined use as predictive biomarkers is especially useful in women, but not in participants with IFG/IGT.