Research in maize is often performed using inbred lines that can be readily transformed, such as B104. However, because the B104 line flowers late, the kernels do not always mature before the end of the growing season, hampering routine seed yield evaluations of biotech traits introduced in B104 at many geographical locations. Therefore, we generated five hybrids by crossing B104 with the early-flowering inbred lines CML91, F7, H99, Mo17, and W153R and showed in three consecutive years that the hybrid lines proved to be suitable to evaluate seed yield under field conditions in a temperate climate. By assessing the two main processes driving maize leaf growth, being rate of growth (leaf elongation rate or LER) and the duration of growth (leaf elongation duration or LED) in this panel of hybrids, we showed that leaf growth heterosis was mainly the result of increased LER and not or to a lesser extent of LED. Ectopic expression of the transgenes GA20-oxidase (GA20-OX) and PLASTOCHRON1 (PLA1), known to stimulate the LER and LED, respectively, in the hybrids showed that leaf length heterosis can be stimulated by increased LER, but not by LED, indicating that LER rather than LED is the target for enhancing leaf growth heterosis.

To investigate a possible direct, growth hormone-releasing, hormone-independent action of a growth hormone secretagogue, GHRP-2, in pituitary somatotroph cells in the presence of inactive growth hormone-releasing hormone receptors.

A range of bone abnormalities including short stature have been reported to be associated with the use of antiepileptic drugs (AEDs) in children. Exactly how AEDs impact skeletal growth, however, is not clear. In the present study, rat growth plate chondrocytes were cultured to study the effects of AEDs, including valproic acid (VPA), oxcarbazepine (OXA), levetiracetam (LEV), lamotrigine (LTG), and topiramate (TPM) on the skeletal growth. VPA markedly reduced the number of chondrocytes by apoptosiswhile other AEDs had no effect. The apoptosis associated noncleaved and cleaved caspase 3, and caspases were increased by exposure to VPA, which up-regulated cyclooxygenase 2 (COX-2) mRNA and protein levels likely through histone acetylation. The COX-2 inhibitor NS-398 attenuated the effects of VPA up-regulating COX-2 expression and decreased VPA-induced caspase 3 expression. The use of VPA in children should be closely monitored or replaced, where appropriate, by AEDs which do not apparently affect the growth plate chondrocytes.

The fibroblast growth factor (FGF) family has various biological functions, including cell growth, tissue regeneration, embryonic development, metabolism, and angiogenesis. In the case of hair growth, several members of the FGF family, such as FGF1 and FGF2, are involved in hair growth, while FGF5 has the opposite effect. In this study, the regulation of the hair growth cycle by FGF12 was investigated. To observe its effect, the expression of FGF12 was downregulated in mice and outer root sheath (ORS) by siRNA transfection, while FGF12 overexpression was carried out using FGF12 adenovirus. For the results, FGF12 was primarily expressed in ORS cells with a high expression during the anagen phase of hair follicles. Knockdown of FGF12 delayed telogen-to-anagen transition in mice and decreased the hair length in vibrissae hair follicles. It also inhibited the proliferation and migration of ORS cells. On the contrary, FGF12 overexpression increased the migration of ORS cells. FGF12-overexpressed ORS cells induced the telogen-to-anagen transition in the animal model. In addition, FGF12 overexpression regulated the expression of PDGF-CC, MDK, and HB-EGF, and treatment of these factors exhibited hair growth promotion. Altogether, FGF12 promoted hair growth by inducing the anagen phase of hair follicles, suggesting the potential for hair loss therapy.

Osteosarcoma (OS) is the primary bone malignancy in children and adolescents, with a high incidence of lung metastasis and poor prognosis. Here, we report that growth hormone receptor (GHR) is overexpressed in OS samples compared with osteofibrous dysplasia. We subsequently demonstrated that GHR knockdown inhibited colony formation, promoted cell apoptosis and decreased the number of cells at G2/M phase in 143B and U2OS cells. Furthermore, knockdown of GHR inhibited tumor growth in vivo. Together, these findings indicate that GHR modulates cell proliferation and metastasis through the phosphoinositide 3-kinase/AKT signaling pathway and may be suitable for use as a putative biomarker of OS.

Growth hormone transduction defect (GHTD) is characterized by severe short stature, impaired STAT3 (signal transducer and activator of transcription-3) phosphorylation and overexpression of the cytokine inducible SH2 containing protein (CIS) and p21/CIP1/WAF1. To investigate the role of p21/CIP1/WAF1 in the negative regulation of the growth hormone (GH)/GH receptor and Epidermal Growth Factor (EGF)/EGF Receptor pathways in GHTD.

Two muscle insulin-like growth factor-I (IGF-I) mRNA splice variants (IGF-IEa and IGF-IEb) have been identified in rodents. IGF-IEb, also called mechano growth factor (MGF) has been found to be upregulated by exercise or muscle damage. Growth hormone (GH) is the principal regulator of IGF-I expression in several tissues including skeletal muscle. Therefore, we investigated the effect of chronic GH excess or disruption of GH receptor (GHR) signalling, and the acute effect of GH administration on expression of muscle IGF-I isoforms using transgenic mice that express bovine GH (bGH), GHR gene-disrupted (GHR-/-) mice and GH-deficient lit/lit mice before and after exogenous GH administration. MGF mRNA in skeletal muscle was increased in bGH mice whereas it was decreased in GHR-/- mice compared with control animals. Exogenous GH administration to dwarf lit/lit mice significantly increased muscle MGF but not IGF-IEa mRNA 4 h after treatment. Twelve hours after GH treatment, both MGF and IGF-IEa mRNAs in muscle were increased compared with vehicle-treated lit/lit mice. In contrast in GH-sufficient lit/+ mice, both MGF and IGF-IEa mRNAs were increased 4 h after and returned to the basal level 12 h after GH treatment. Hepatic IGF-I isoforms were regulated in parallel by GH. Thus, our results demonstrated that: (1) MGF mRNA in skeletal muscle is expressed in parallel with GH action; (2) MGF mRNA in muscle is produced preferentially in the situation of GH deficiency in contrast to the pattern in the GH-sufficient state; and (3) the induction of IGF-I isoforms by GH is tissue-specific.

The data presented in this data paper describe the early growth of cover crop cultivated in growth chamber under non-limiting conditions. Seventeen species of four botanical groups were described after one month of growth. Traits related to plant growth and leaf area development were measured (five traits) and calculated (eight traits). This data set is made available to enable comparisons between dataset, extended analysis and meta-analysis on cover crop traits. The data presented in this article were used on the research article entitled "Leaf area development strategies of cover plants used in banana plantations identified from a set of plant traits' [1].

High vascular endothelial growth factor (VEGFA) levels at the time of diagnosis confer a worse prognosis to multiple malignancies. Our aim was to investigate the role of VEGFA in promoting tumour growth through interaction with its environment.

Fluoroquinolones (FQs), commonly known for their antibiotic properties, exhibit additional pharmacological potential with anti-proliferative effects on various malignant cell types and immunomodulatory responses. Despite these observed effects, the precise mechanisms of action remain elusive. This study elucidates the biological impact of FQs on insulin-like growth factor-binding protein 3 (IGFBP-3) productions in a p53-dependent manner. Cultured cells and mouse models treated with FQs demonstrated increased IGFBP-3 mRNA expression and protein secretion. The FQ-induced IGFBP-3 was identified to impede cell growth by inhibiting IGF-I signaling and exerting effects through an IGF-independent pathway. Notably, FQ-mediated suppression of cell proliferation was reversed in p53-null and p53 knockdown cells, suggesting the pivotal role of p53 in FQ-induced IGFBP-3 production and IGFBP-3-mediated growth inhibition. Additionally, ciprofloxacin, a clinically used FQ, exhibited the induction of tumor cell apoptosis and attenuation of tumor growth in a syngeneic mouse hepatocellular carcinoma (HCC) model. These findings unveil a novel mechanism through which FQs act as anti-proliferative agents, prompting further exploration of their potential utility or derivative compounds in cancer treatment and prevention.

Maturation of the mammalian growth axis is thought to be linked to the transition from fetal to post-natal life at birth. However, in an altricial marsupial, the tammar wallaby (Macropus eugenii), this process occurs many months after birth but at a time when the young is at a similar developmental stage to that of neonatal eutherian mammals. Here we manipulate growth rates and demonstrate in slow, normal and fast growing tammar young that nutrition and growth rate affect the time of maturation of the growth axis. Maturation of GH/IGF-I axis components occurred earlier in fast growing young, which had significantly increased hepatic GHR, IGF1 and IGFALS expression, plasma IGF-I concentrations, and significantly decreased plasma GH concentrations compared to age-matched normal young. These data support the hypothesis that the time of maturation of the growth axis depends on the growth rate and maturity of the young, which can be accelerated by changing their nutritional status.

Objective: The aim of this study was to study growth patterns of children born after suspected fetal growth restriction (FGR) at term and to compare the effect of induction of labor (IoL) and expectant management (EM), also in relation to neurodevelopmental and behavioral outcome at age 2. Methods: We performed a 2 years' follow-up of growth of children included in the Disproportionate Intrauterine Growth Restriction Trial at Term (DIGITAT) study, a Randomized Controlled Trial (RCT) comparing IoL with EM in pregnancies with suspected FGR at term. We collected data on child growth until the age of 2 years. Standard deviation scores (SDSs) for height and weight were calculated at different ages. We assessed the effects of IoL compared with EM and the effects of a birth weight below or above the 3rd or 10th centile on catch-up growth. Target height SDSs were calculated using the height of both parents. Results: We found a significant increase in SDS in the first 2 years. Children born after EM showed more catch-up growth in the first month [height: mean difference -0.7 (95% CI: 0.2; 1.3)] and weight [mean difference -0.5 (95% CI: 0.3; 0.7)]. Children born with a birth weight below the 3rd and 10th centiles showed more catch-up growth after 1 year [mean difference -0.8 SDS (95% CI: -1.1; -0.5)] and after 2 years [mean difference -0.7 SDS (95% CI: -1.2; -0.2)] as compared to children with a birth weight above the 3rd and 10th centiles. SDS at birth had the strongest effect on adverse neurodevelopmental outcome at 2 years of age. Conclusion: After FGR at term, postnatal catch-up growth is generally present and associated with the degree of FGR. Obstetric management in FGR influences postnatal growth. Longer-term follow-up is therefore needed and should be directed at growth and physical health. Clinical Trial Registration: www.ClinicalTrials.gov, identifier SRCTN10363217.

Many tip-growing cells are capable of responding to guidance cues, during which cells precisely steer their growth toward the source of guidance signals. Though several players in signal perception have been identified, little is known about the downstream signaling that controls growth direction during guidance. Here, using combined modeling and experimental studies, we demonstrate that the growth guidance of Arabidopsis pollen tubes is regulated by the signaling network that controls tip growth. Tip-localized exocytosis plays a key role in this network by integrating guidance signals with the ROP1 Rho GTPase signaling and coordinating intracellular signaling with cell wall mechanics. This model reproduces the high robustness and responsiveness of pollen tube guidance and explains the connection between guidance efficiency and the parameters of the tip growth system. Hence, our findings establish an exocytosis-coordinated mechanism underlying the cellular pathfinding guided by signal gradients and the mechanistic linkage between tip growth and guidance.

Mammalian postnatal growth is regulated primarily by the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis. MafB is a basic leucine zipper (bZip) transcription factor that has pleiotropic functions. Although MafB plays a critical role in fetal brain development, such as in guidance for hindbrain segmentation, its postnatal role in neurons remains to be elucidated. To investigate this, we used neuron-specific Mafb conditional knockout (cKO) mice. In addition to an approximately 50% neonatal viability, the Mafb cKO mice exhibited growth retardation without apparent signs of low energy intake. Notably, serum IGF-I levels of these mice in the postnatal stage were lower than those of control mice. They seemed to have a neuroendocrine dysregulation, as shown by the upregulation of serum GH levels in the resting state and an inconsistent secretory response of GH upon administration of growth hormone-releasing hormone. These findings reveal that neuronal MafB plays an important role in postnatal development regulated by the GH/IGF-I axis.

Growth control in animals and plants involves mobile signals. Depending on their range of action, these signals coordinate the growth of cells within an organ or the growth of different organs in a larger, functionally integrated structure. In plants, flowers are such integrated structures, yet it remains poorly understood how growth of the constituent organs is coordinated to ensure their correct relative sizes. The cytochrome P450 KLUH/CYP78A5 and its homolog CYP78A7 promote organ growth via a non-cell-autonomous signal; however, the range of this signal and thus its developmental function are unknown. Here we use a system for the predictable generation of chimeric plants to determine the range of the KLUH-dependent signal. In contrast with the largely autonomous behavior of another tested growth-control gene, we find that KLUH activity extends beyond individual organs and flowers. Its overall activity is integrated across an inflorescence to determine final organ size, which is largely independent of the genotype of the individual organs. Thus, the KLUH-dependent signal appears to move beyond individual organs in a flower, providing a mechanism for coordinating their growth and ensuring floral symmetry as an important determinant of a plant's attractiveness to pollinators.

Delirium is a common disorder in elderly medical inpatients with serious adverse outcomes and is characterized by sudden onset, disturbance in attention, awareness, consciousness and cognition, and often with behavioural disturbances. Central to understanding delirium, is understanding mechanisms by which body and brain wellbeing are linked and in particular how brain responses to bodily homeostatic stress is mediated. A number of studies have investigated the relationship between insulin-like growth factor I (IGF-I) and delirium in medically ill hospitalised patients with conflicting results. However, none have investigated growth hormone (GH) which is related to IGF-I via negative feedback.

Rapamycin, an immunosuppressant agent used in renal transplantation with antitumoral properties, has been reported to impair longitudinal growth in young individuals. As growth hormone (GH) can be used to treat growth retardation in transplanted children, we aimed this study to find out the effect of GH therapy in a model of young rat with growth retardation induced by rapamycin administration. Three groups of 4-week-old rats treated with vehicle (C), daily injections of rapamycin alone (RAPA) or in combination with GH (RGH) at pharmacological doses for 1 week were compared. GH treatment caused a 20% increase in both growth velocity and body length in RGH animals when compared with RAPA group. GH treatment did not increase circulating levels of insulin-like growth factor I, a systemic mediator of GH actions. Instead, GH promoted the maturation and hypertrophy of growth plate chondrocytes, an effect likely related to AKT and ERK1/2 mediated inactivation of GSK3β, increase of glycogen deposits and stabilization of β-catenin. Interestingly, GH did not interfere with the antiproliferative and antiangiogenic activities of rapamycin in the growth plate and did not cause changes in chondrocyte autophagy markers. In summary, these findings indicate that GH administration improves longitudinal growth in rapamycin-treated rats by specifically acting on the process of growth plate chondrocyte hypertrophy but not by counteracting the effects of rapamycin on proliferation and angiogenesis.

Fibrosarcomas are soft tissue mesenchymal tumors originating from transformed fibroblasts. Fibroblast growth factor-2 (FGF2) and its tyrosine-kinase receptors (FGFRs) play pivotal roles in fibrosarcoma onset and progression, FGF2 being actively produced by fibroblasts in all stages along their malignant transformation to the fibrosarcoma stage. The soluble pattern recognition receptor long pentraxin-3 (PTX3) is an extrinsic oncosuppressor whose expression is reduced in different tumor types, including soft tissue sarcomas, via hypermethylation of its gene promoter. PTX3 interacts with FGF2 and other FGF family members, thus acting as a multi-FGF antagonist able to inhibit FGF-dependent neovascularization and tumor growth. Here, PTX3 overexpression significantly reduced the proliferative and tumorigenic potential of fibrosarcoma cells in vitro and in vivo. In addition, systemic delivery of human PTX3 driven by the Tie2 promoter inhibited the growth of fibrosarcoma grafts in transgenic mice. In a translational perspective, the PTX3-derived small molecule FGF trap NSC12 prevented activation of the FGF/FGFR system in fibrosarcoma cells and reduced their tumorigenic activity in vivo. In conclusion, impairment of the FGF/FGFR system by FGF trap molecules may represent a novel therapeutic approach for the treatment of fibrosarcoma.

Basic fibroblast growth factor immunoreactivity (bFGF-IR) was detected in a specific set of nerve cells in the central nervous system of the gull-tapeworm Diphyllobothrium dendriticum (Cestoda)--an obligatory endoparasite. The long varicose processes of the bFGF-IR neurons extend along the two main nerve cords, which contain an actively growing population of nerve cells. A neurotrophic function for the bFGF-like material is proposed. The adult tapeworm lives in the intestine of a homeothermic host and has a pattern of very active and never ending growth. The larval stages live in poikilothermic hosts and grow very slowly. The bFGF-IR nerve cells occur both in II stage larvae and in adult worms. Thus, no correlation between the presence of bFGF-IR and the general growth rate of the worm was found. Western blot analysis revealed the presence of an anti-bFGF immunoreactive peptide with a molecular mass of 47 kDa in both larval and adult worms.

Many tumors produce platelet-derived growth factor (PDGF)-DD, which promotes cellular proliferation, epithelial-mesenchymal transition, stromal reaction, and angiogenesis through autocrine and paracrine PDGFRβ signaling. By screening a secretome library, we found that the human immunoreceptor NKp44, encoded by NCR2 and expressed on natural killer (NK) cells and innate lymphoid cells, recognizes PDGF-DD. PDGF-DD engagement of NKp44 triggered NK cell secretion of interferon gamma (IFN)-γ and tumor necrosis factor alpha (TNF-α) that induced tumor cell growth arrest. A distinctive transcriptional signature of PDGF-DD-induced cytokines and the downregulation of tumor cell-cycle genes correlated with NCR2 expression and greater survival in glioblastoma. NKp44 expression in mouse NK cells controlled the dissemination of tumors expressing PDGF-DD more effectively than control mice, an effect enhanced by blockade of the inhibitory receptor CD96 or CpG-oligonucleotide treatment. Thus, while cancer cell production of PDGF-DD supports tumor growth and stromal reaction, it concomitantly activates innate immune responses to tumor expansion.