Natural polymorphism of ZmICE1 contributes to amino acid metabolism that impacts cold tolerance in maize.

Cold stress negatively affects maize (Zea mays L.) growth, development and yield. Metabolic adjustments contribute to the adaptation of maize under cold stress. We show here that the transcription factor INDUCER OF CBF EXPRESSION 1 (ZmICE1) plays a prominent role in reprogramming amino acid metabolome and COLD-RESPONSIVE (COR) genes during cold stress in maize. Derivatives of amino acids glutamate/asparagine (Glu/Asn) induce a burst of mitochondrial reactive oxygen species, which suppress the cold-mediated induction of DEHYDRATION RESPONSE ELEMENT-BINDING PROTEIN 1 (ZmDREB1) genes and impair cold tolerance. ZmICE1 blocks this negative regulation of cold tolerance by directly repressing the expression of the key Glu/Asn biosynthesis genes, ASPARAGINE SYNTHETASEs. Moreover, ZmICE1 directly regulates the expression of DREB1s. Natural variation at the ZmICE1 promoter determines the binding affinity of the transcriptional activator ZmMYB39, a positive regulator of cold tolerance in maize, resulting in different degrees of ZmICE1 transcription and cold tolerance across inbred lines. This study thus unravels a mechanism of cold tolerance in maize and provides potential targets for engineering cold-tolerant varieties.

Metabolic remodeling maintains a reducing environment for rapid activation of the yeast DNA replication checkpoint.

Nucleotide metabolism fuels normal DNA replication and is also primarily targeted by the DNA replication checkpoint when replication stalls. To reveal a comprehensive interconnection between genome maintenance and metabolism, we analyzed the metabolomic changes upon replication stress in the budding yeast S. cerevisiae. We found that upon treatment of cells with hydroxyurea, glucose is rapidly diverted to the oxidative pentose phosphate pathway (PPP). This effect is mediated by the AMP-dependent kinase, SNF1, which phosphorylates the transcription factor Mig1, thereby relieving repression of the gene encoding the rate-limiting enzyme of the PPP. Surprisingly, NADPH produced by the PPP is required for efficient recruitment of replication protein A (RPA) to single-stranded DNA, providing the signal for the activation of the Mec1/ATR-Rad53/CHK1 checkpoint signaling kinase cascade. Thus, SNF1, best known as a central energy controller, determines a fast mode of replication checkpoint activation through a redox mechanism. These findings establish that SNF1 provides a hub with direct links to cellular metabolism, redox, and surveillance of DNA replication in eukaryotes.

Association between serum glucose level and spot sign in intracerebral hemorrhage.

Hyperglycemia was proved to cause neuron death in both animal experiments and poor outcome of hemorrhage patients, but the predictive ability of admission blood glucose level for early hematoma growth in patients with intracranial hemorrhage (ICH) is still controversial. Spot sign is a well-established imaging predictor for early hematoma growth, implying active microvascular bleeding. Here, we aim to assess associations between admission serum glucose and early hematoma expansion in ICH patients, as well as spot sign.We retrospectively reviewed all the patients with ICH from January 2017 to March 2018 in West China Hospital, Sichuan University. Admission blood glucose, clinical variables, radiological characteristics, and laboratorial parameters were obtained from medical record. According to computed tomography (CT) and computed tomography angiography (CTA) scan results, hematoma expansion and spot sign were identified by 2 experienced neuroradiologists. Multivariate logistic regression analyses were employed to adjust the associations of hematoma expansion and spot sign with other clinical parameters.Around 42 patients exhibited early hematoma expansions and 26 exhibited spot signs over 138 enrolled patients. The average level of admission blood glucose was 7.55 mmol/L. Multivariate logistic regression analyses revealed that Glasgow Coma Scale (GCS) score on admission, hematoma volume, spot sign, and hyperglycemia were associated with hematoma expansion, whereas admission serum glucose and hematoma size were only associated with spot sign, respectively.Admission blood glucose level is correlated with hematoma growth and incidence of spot sign. These results indicated that hyperglycemia probably plays a critical role in the pathological process of the active bleeding. Further studies should be drawn urgently to understand the potential molecular mechanism of systemic hyperglycemia in affecting prognosis of patients with ICH.

Predictive Accuracy of Neutrophil-to-Lymphocyte Ratio on Long-Term Outcome in Patients with Spontaneous Intracerebral Hemorrhage.

BACKGROUND: It is well established that inflammation plays a critical role in the progression of intracerebral hemorrhage (ICH). Recently the neutrophil-to-lymphocyte ratio (NLR) was identified as a predictor for the short-term outcome in ICH patients. However, the association of NLR with the long-term outcome in patients with ICH remains unknown. Here, we aimed to assess the relationship between NLR and the long-term prognosis in ICH patients. METHODS: All patients with spontaneous ICH who were hospitalized at West China Hospital of Sichuan University from October 2013 to May 2017 were retrospectively enrolled. White blood count, absolute count of neutrophils, and lymphocytes were extracted from electronic medical records, and NLR was calculated according to admission neutrophil count (ANC) and lymphocyte count (ALC). The associations between long-term outcomes and laboratory biomarkers were estimated by multivariable logistic regression analysis. Receiver operating characteristic (ROC) curves were also determined to compare the predictive powers between each inflammatory factor. RESULTS: A total of 481 ICH patients were included in the study. Of those, 204 presented with unfavorable outcomes, and 142 were dead within 6 months. Age, Glasgow Coma Scale (GCS) scores, WBC, ANC, NLR, hematoma size, and hydrocephalus were independently associated with poor prognosis of ICH. Multiple linear analysis showed GCS, hematoma volume, WBC, ANC, and ALC to be correlated with NLR. Moreover, in comparison with other single laboratory determinations, NLR also showed better predictive capacity for long-term mortality and morbidity, for which the best predictive cutoff values were 9.07 and 8.69, respectively. CONCLUSIONS: NLR independently predicts 180-day morbidity and 180-day mortality in patients with spontaneous ICH.

The comparative study of island sign and the spot sign in predicting short-term prognosis of patients with intracerebral hemorrhage.

OBJECTIVES: It is well known that early hematoma expansion is associated with short-term prognosis of patients with intracranial hemorrhage (ICH). And spot sign is recognized as a reliable computed tomography angiography (CTA) predictor for early hematoma expansion. Recently, island sign is also reported as a novel computed tomography (CT) predictor for early hematoma growth. Here, we compared the predictive abilities of these two signs for short-term outcomes of ICH patients. PATIENTS AND METHODS: All the ICH patients were retrospectively identified. Clinical characteristics and radiological parameters were obtained from electronic medical records. Hematoma expansion, spot sign and island sign were assessed by two senior neurologists according to the initial and follow-up CT scans. 3-months prognoses were estimated according to Glasgow outcome scale (GOS). Multivariate logistic regression analyses were employed to explore the associations of short-term prognosis on island sign, spot sign and other clinical variables. RESULTS: There were 283 ICH patients included. 113 of them presented with early hematoma expansions. 66 of them exhibited island sign, while spot sign occurred in 85 patients. Univariate analyses demonstrated that GCS score at admission (OR: 0.464, 95%CI: 0.395-0.547), hematoma volume (OR:1.062, 95%CI: 1.041-1.083), interventricular extension(OR:9.528, 95%CI: 3.915-23.187), island sign (OR: 4.595, 95%CI: 2.404-8.784) and spot sign (OR: 4.052, 95%CI: 2.297-7.147) were correlated with 3-months morbidity. Moreover, multivariate logistic regression analyses further revealed that both spot sign (OR: 3.413, 95%CI: 1.570-7.422) and island sign (OR: 7.564, 95%CI: 2.969-19.273) were strongly associated with 3-months poor outcome and have comparable predictive values (AUC: 0.636 vs. 0.622, P = .58). However, spot sign exhibited a superior predictive ability for 3-months mortality compared to island sign (OR: 2.713, 95%CI: 1.570-4.217 vs. OR: 2.362, 95%CI: 1.238-3.899, AUC: 0.700 vs. 0.603, P < .01). CONCLUSIONS: Island sign is not just a convenient and reliable predictor for short-term prognosis of ICH patients, but also could be used as an indicator for accurate diagnosis and aggressive treatment.