Follistatin binds and neutralizes members of the TGFbeta superfamily including activin, myostatin, and growth and differentiation factor 11 (GDF11). Crystal structure analysis of the follistatin-activin complex revealed extensive contacts between follistatin domain (FSD)-2 and activin that was critical for the high-affinity interaction. However, it remained unknown whether follistatin residues involved with myostatin and GDF11 binding were distinct from those involved with activin binding. If so, this would allow development of myostatin antagonists that would not inhibit activin actions, a desirable feature for development of myostatin antagonists for treatment of muscle-wasting disorders. We tested this hypothesis with our panel of point and domain swapping follistatin mutants using competitive binding analyses and in vitro bioassays. Our results demonstrate that activin binding and neutralization are mediated primarily by FSD2, whereas myostatin binding is more dependent on FSD1, such that deletion of FSD2 or adding an extra FSD1 in place of FSD2 creates myostatin antagonists with vastly reduced activin antagonism. However, these mutants also bind GDF11, indicating that further analysis is required for creation of myostatin antagonists that will not affect GDF11 activity that could potentially elicit GDF11-induced side effects in vivo.

The driving mechanism for the wintertime (December–March) Aleutian Low–Icelandic Low (AL‐IL) seesaw is investigated with National Centers for Environmental Prediction/National Center for Atmospheric Research reanalysis data for 1948–2009. It is shown that the AL and the IL are dynamically linked through the eastern Pacific wave train (EPW) and that both the EPWs and the stratospheric polar vortex are found to work cooperatively to produce a significant AL‐IL seesaw. In general, it is found that wave reflection by the polar vortex is crucial for the formation of the AL‐IL seesaw. However, when the EPWs are extremely strong, the AL‐IL seesaw appears to be caused primarily by horizontal wave propagation. It is further shown that the Pacific center of the traditional Arctic Oscillation pattern is present when the AL‐IL seesaw is active, but it disappears when the AL‐IL seesaw is absent.

Comparing outcomes related to dialysis modality is complicated by selection bias introduced by patients and physicians. To address the impact of selection bias, this study compared mortality by initial dialysis modality among patients who had ESRD and were placed on the transplant waiting list. This study was a historical prospective cohort of 12,568 patients in the United States who initiated dialysis between May 1, 1995, and October 31, 1998, and were placed on the transplant waiting list before dialysis initiation. Two-year mortality was compared using Kaplan-Meier curves and Cox proportional hazards models that analyzed patients primarily using an intention-to-treat approach and separately censored patients on a modality switch. At 2 yr, the unadjusted mortality rate was 6.6% among peritoneal dialysis (PD) patients compared with 6.9% among hemodialysis (HD) patients (hazard ratio [HR] 1.01; 95% confidence interval [CI] 0.82 to 1.23). After controlling for differences in baseline characteristics, comorbidities, and laboratory variables, the selection of PD versus HD remained associated with a similar 2-yr mortality risk (HR 1.03; 95% CI 0.83 to 1.28). In separate models, 2-yr mortality associated with PD versus HD was significant among patients with body mass index (BMI) >26 kg/m 2 (HR 1.37; 95% CI 1.01 to 1.83) but not among patients with BMI <26 kg/m 2 (HR 0.81; 95% CI 0.61 to 1.07). Results were similar after censoring on a modality switch. In conclusion, although choice of initial dialysis modality seems to be associated with equivalent outcomes among patients who have ESRD and are placed on the transplant waiting list, patients with BMI >26 kg/m 2 have increased 2-yr mortality associated with the selection of PD versus HD. Because the interpretation of observational data is highly affected by residual confounding and selection bias, further efforts should focus on the formation and testing of hypotheses to improve dialysis delivery.

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Stroke is the second most common cause of mortality worldwide and the first leading cause of death and disability in China.1,2 According to the World Health Organization report, the incidence of stroke in China is growing at an annual rate of 8.7%, and this trend will most likely continue during the next 3 decades. 3,4 It is well known that early identification of risk factors for stroke would allow for effective preventive strategies and reduced economic burden. Some well-established stroke risk factors, including hypertension, diabetes mellitus, coronary artery disease, smoking, physical inactivity, and obesity have been identified 5 ; however, it is also necessary to investigate more potential risk factors.Major depression, a serious psychiatric disorder affecting ≈16% of the general population, 6 is a known risk factor for vascular diseases, such as coronary heart disease and myocardial infarction. 7,8 It is worth noting that several researches including prospective studies have investigated the associations between depressive disorder and the occurrence of stroke, but they have yielded mixed results. For example, a recent large cohort study with 80 574 participants showed an increased stroke risk in women with a previous diagnosis of depression, 9 but other several studies found no evidence of depression being a significant risk factor for cerebrovascular diseases 10,11 or showed an increased stroke risk only in participants >65 years of age.12 These conflicting findings from the existing studies may be because of a limited sample size, a short follow-up duration, or the use of self-reported symptom scales, rather than diagnostic instruments to assess depressive Background and Purpose-Although the relationship between depression and stroke risk has been investigated, findings in previous reports were conflicting. The aim of this study was to prospectively examine the effect of major depressive episodes (MDE) on stroke incidence and further assess the potential dose-response relationship between number of depression symptoms and subsequent stroke risk in Chinese population. Methods-A total of 199 294 men and 288 083 women aged 30 to 79 years without a history of stroke, heart disease, and cancer in the China Kadoorie Biobank cohort were followed from 2004 to 2013. A World Health Organization Composite International Diagnostic Interview-Short Form was used to access MDE according to Diagnostic and Statistical Manual of Mental Disorders-IV criteria. Stroke events were ascertained through death certificates, medical records, and health insurance data. Results-Past year MDE was marginally associated with a 15% increased risk of stroke (adjusted hazard ratio, 1.15; 95% confidence interval, 0.99-1.33) in the fully adjusted model, and the association was steeper and statistically significant in individuals aged <50 years, smokers, drinkers, those with higher education degree, body mass index <24.0 kg/m 2 , and no history of diabetes mellitus. Moreover, there was a positive dose-response relationship between the num...

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Background: Members of the AT-HOOK MOTIF CONTAINING NUCLEAR LOCALIZED ( AHL ) family are involved in various plant biological processes via protein-DNA and protein-protein interaction. However, no the systematic identification and analysis of AHL gene family have been reported in cotton. Results: To investigate the potential functions of AHLs in cotton, genome-wide identification, expressions and structure analysis of the AHL gene family were performed in this study. 48, 51 and 99 AHL genes were identified from the G.raimondii, G.arboreum and G.hirsutum genome, respectively. Phylogenetic analysis revealed that the AHLs in cotton evolved into 2 clades, Clade-A with 4-5 introns and Clade-B with intronless (excluding AHL 20-2). Based on the composition of the AT-hook motif(s) and PPC/DUF 296 domain, AHL proteins were classified into three types (Type-I/-II/-III), with Type-I AHLs forming Clade-B, and the other two types together diversifying in Clade-A. The detection of synteny and collinearity showed that the AHLs expanded with the WGD in cotton, and the sequence structure of AHL20-2 showed the tendency of increasing intron in three different Gossypium spp . The ratios of non-synonymous (Ka) and synonymous (Ks) substitution rates of orthologous gene pairs revealed that the AHL genes of G.hirsutum had undergone through various selection pressures, purifying selection mainly in A-subgenome and positive selection mainly in D-subgenome. Examination of their expression patterns showed most of AHLs of Clade-B expressed predominantly in stem, while those of Clade-A in ovules, suggesting that the AHLs within each clade shared similar expression patterns with each other. qRT-PCR analysis further confirmed that some GhAHLs higher expression in stems and ovules. Conclusion: In this study, 48, 51 and 99 AHL genes were identified from three cotton genomes respectively. AHLs in cotton were classified into two clades by phylogenetic relationship and three type based on the composition of motif and domain. The AHLs expanded with segmental duplication, not tandem duplication. The expression profiles of GhAHLs revealed abundant differences in expression levels in various tissues and at different stages of ovules development. Our study provided significant insights into the potential functions of AHLs in regulating the growth and development in cotton.

BACKGROUNDSweet potato often suffers mechanical damage during harvest, handling, and transportation. Infections, water loss, and quality changes of sweet potato caused by mechanical damage pose great financial losses. Wound healing is an effective method to alleviate such problems. In this study, the effects of postharvest treatment with benzothiazole (BTH) on wound healing of sweet potato was investigated.RESULTSPostharvest BTH treatment of sweet potatoes promoted lignin accumulation in wounded tissues, and 100 mg L−1 BTH exhibited better effects than 50 mg L−1 or 150 mg L−1 BTH. The biosynthesis of lignin in wounded tissues significantly decreased the weight loss of sweet potatoes. An increase in respiration intensity after BTH treatment was observed. The total phenolic and flavonoid contents and the activity of phenylalanine ammonia‐lyase, peroxidase, and polyphenol oxidase were increased in BTH‐treated sweet potatoes. This suggests that BTH increases phenylpropanoid metabolism.CONCLUSIONPostharvest 100 mg L−1 BTH treatment could promote wound healing in mechanically damaged sweet potatoes. The activation of the phenylpropanoid metabolism might be the mechanism of action of BTH in wound healing. © 2020 Society of Chemical Industry