CCT domain-containing genes generally control flowering in plants. Currently, only six of the 41 CCT family genes have been confirmed to control flowering in rice. To efficiently identify more heading date-related genes from the CCT family, we compared the positions of heading date QTLs and CCT genes and found that 25 CCT family genes were located in the QTL regions. Association mapping showed that a total of 19 CCT family genes were associated with the heading date. Five of the seven associated genes within QTL regions and two of four associated genes outside of the QTL regions were confirmed to regulate heading date by transformation. None of the seven non-associated genes outside of the QTL regions regulates heading date. Obviously, combination of candidate gene-based association mapping with linkage analysis could improve the identification of functional genes. Three novel CCT family genes, including one non-associated (OsCCT01) and two associated genes (OsCCT11 and OsCCT19) regulated the heading date. The overexpression of OsCCT01 delayed flowering through suppressing the expression of Ehd1, Hd3a and RFT1 under both long day and short day conditions. Potential functions in regulating heading date of some untested CCT family genes were discussed.

miRNAs play an important role in the processes of cell differentiation, biological development, and physiology. Here we investigated the molecular mechanisms regulating milk secretion and quality in dairy cows via transcriptome analyses of mammary gland tissues from dairy cows during the high-protein/high-fat, low-protein/low-fat or dry periods. To characterize the important roles of miRNAs and mRNAs in milk quality and to elucidate their regulatory networks in relation to milk secretion and quality, an integrated analysis was performed. A total of 25 core miRNAs were found to be differentially expressed (DE) during lactation compared to non-lactation, and these miRNAs were involved in epithelial cell terminal differentiation and mammary gland development. In addition, comprehensive analysis of mRNA and miRNA expression between high-protein/high-fat group and low-protein/low-fat groups indicated that, 38 miRNAs and 944 mRNAs were differentially expressed between them. Furthermore, 38 DE miRNAs putatively negatively regulated 253 DE mRNAs. The putative genes (253 DE mRNAs) were enriched in lipid biosynthetic process and amino acid transmembrane transporter activity. Moreover, putative DE genes were significantly enriched in fatty acid (FA) metabolism, biosynthesis of amino acids, synthesis and degradation of ketone bodies and biosynthesis of unsaturated FAs. Our results suggest that DE miRNAs might play roles as regulators of milk quality and milk secretion during mammary gland differentiation.

PiT2 is a member of the inorganic phosphate transporter family, and is extensively expressed in the nervous system. It was found that loop7 domain of PiT2 is not required for retroviral recognition and transport function. The exact functions of loop7 remain poorly understood. Here we show that loop7 of PiT2 is necessary for the transport of PiT2 protein to the cell surface. Further, loop7 is also related to the outgrowth of neurite in Neuro2A cells interacts with the light chain 1 of microtubule-associated protein 1B (MAP1B). PiT2 with mutated MAP1B binding sites affect neurite outgrowth whereas Pi transport function deficient mutants of PiT2 do not. We also show that Drosophila dPiT interacts with microtubule-associated protein Futsch, and dPiT is crucial for the normal development of neuromuscular junctions (NMJs). These results indicate that PiT2 might participate in the regulation of neuronal outgrowth by interacting with MAP1B and independently of its Pi transport function in the nervous system.

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disease characterized by varying degrees of oculocutaneous albinism, recurrent infections, and a mild bleeding tendency, with late neurologic dysfunction. This syndrome is molecularly characterized by pathognomonic mutations in the LYST (lysosomal trafficking regulator). Using whole genome sequencing (WGS) we attempted to identify novel mutations of CHS based on a family of CHS with atypical symptoms. The two patients demonstrated a phenotypic constellation including partial oculocutaneous albinism, frequency upper respiratory infection or a marginal intelligence, without bleeding tendency and severe immunodeficiency. WGS revealed two compound LYST mutations including a maternally inherited chr1:235969126G > A (rs80338652) and a novel paternally inherited chr1: 235915327A > AT, associated with autosomal recessive CHS. These two variants fall in the coding regions of LYST, resulting in premature truncation of LYST due to R1104X/N2535KfsX2 induced incomplete translation. Notably, the heterozygous carriers (i.e. parents) were unaffected. Our finding also reveals decreased plasma serotonin levels in patients with CHS compared with unaffected individuals for the first time. The present study contributes to improved understanding of the causes of this disease and provides new ideas for possible treatments.

We previously reported on the strong symbiosis of AMF species (Rhizophagus irregularis CD1) with the cotton (Gossypium hirsutum L.) which is grown worldwide. In current study, it was thus investigated in farmland to determine the biological control effect of AMF on phosphorus acquisition and related gene expression regulation, plant growth and development, and a series of agronomic traits associated with yield and fiber quality in cotton. When AMF and cotton were symbiotic, the expression of the specific phosphate transporter family genes and P concentration in the cotton biomass were significantly enhanced. The photosynthesis, growth, boll number per plant and the maturity of the fiber were increased through the symbiosis between cotton and AMF. Statistical analysis showed a highly significant increase in yield for inoculated plots compared with that from the non inoculated controls, with an increase percentage of 28.54%. These findings clearly demonstrate here the benefits of AMF-based inoculation on phosphorus acquisition, growth, seed cotton yield and fiber quality in cotton. Further improvement of these beneficial inoculants on crops will help increase farmers' income all over the world both now and in the future.

A new series of etherification chalcone derivatives were designed and synthesized through Willimison etherification and Claisen-Schmidt condensation. Among them, compound 2-c which was given chemical name of S17, has been successfully screened out as the most potent one on gastric cancer cell line(MGC803) through the investigation for their effects against the growth of five cancer cell lines (EC109, HepG2, MCF7, MGC803, SKNSH). S17 exhibited strong anti-proliferative activity on other two gastric cancer cells (HGC27 and SGC7901), but less cytotoxicity to non-malignant gastric epithelial cells GES1. S17 potently killed gastric cancer cells with causing modulation of Bcl-2 family proteins and activation of caspase 9/3 cascade. S17 also up-regulated DR5 expression and DR5 knockdown partially reversed S17-induced apoptosis, caspase activation and MMP decrease. S17 robustly induced generation of ROS with Keap/Nrf2 pathway activated and the application of ROS scavenger N-acetyl cysteine (NAC) completely blocked these effects by S17 in MGC803 cells. Intraperitoneal administration of S17 significantly inhibited the growth of MGC803 cells in vivo in a xenograft mouse model without observed toxicity. These results indicated that S17 is a leadbrominated chalcone derivate and deserves further investigation for prevention and treatment of gastric cancer.

The growth and development of embryonic skeletal muscle plays a crucial role in sheep muscle mass. But proteomic analyses for embryonic skeletal development in sheep had been little involved in the past research. In this study, we explored differential abundance proteins during embryonic skeletal muscle development by the tandem mass tags (TMT) and performed a protein profile analyses in the longissimus dorsi of Chinese merino sheep at embryonic ages Day85 (D85N), Day105 (D105N) and Day135 (D135N). 5,520 proteins in sheep embryonic skeletal muscle were identified, and 1,316 of them were differential abundance (fold change ≥1.5 and p-value < 0.05). After the KEGG enrichment analyses, these differential abundance proteins were significant enriched in the protein binding, muscle contraction and energy metabolism pathways. After validation of the protein quantification with the parallel reaction monitoring (PRM), 41% (16/39) significant abundance proteins were validated, which was similar to the results of protein quantification with TMT. All results indicated that D85N to D105N was the stage of embryonic muscle fibers proliferation, while D105N to D135N was the stage of their hypertrophy. These findings provided a deeper understanding of the function and rules of proteins in different phases of sheep embryonic skeletal muscle growth and development.

The dysfunction of placenta is common in somatic cell nuclear transfer (SCNT) cloned cattle and would cause aberrant fetal development and even abortion, which occurred with highest rate at the mid- to late gestation. However, the mechanism of abnormal placentas was unclear. To analyze the transcriptome-wide characteristics of abnormal placentas in SCNT cloned cattle, the mRNA, lncRNA and miRNA of placental cotyledon tissue at day 180 after gestation were sequenced. A total of 19,055 mRNAs, 30,141 lncRNAs and 684 miRNAs were identified. Compared with control group, 362 mRNAs, 1,272 lncRNAs and nine miRNAs (six known and three novel miRNAs) were differentially expressed (fold change ≥ 2 and P-value < 0.05). The differentially expressed genes were functionally enriched in urea and ions transmembrane transport, which indicated that the maternal-fetal interactions were disturbed in impaired placentas. Furthermore, the competing endogenous RNAs (ceRNAs) networks were identified to illustrate their roles in abnormal placental morphology. The present research would be helpful to discover the mechanism of late gestational abnormality of SCNT cattle by provides important genomic information and insights.