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Epithelial regeneration is critical for barrier maintenance and organ function after intestinal injury. The intestinal stem cell (ISC) niche provides Wnt, Notch and epidermal growth factor (EGF) signals supporting Lgr5 + crypt base columnar ISCs for normal epithelial maintenance. However, little is known about the regul

Neuropilins (NRPs) are cell surface receptors for vascular endothelial growth factor (VEGF) and SEMA3 (class 3 semaphorin) family members. The role of NRPs in neurons and endothelial cells has been investigated, but the expression and role of NRPs in epithelial cells is much less clear. Herein, the expression and localization of NRP1 was investigated in human and mouse skin and squamous cell carcinomas (SCCs). Results indicated that NRP1 mRNA and protein was expressed in the suprabasal epithelial layers of the skin sections. NRP1 staining did not overlap with that of keratin 14 (K14) or proliferating cell nuclear antigen, but did co-localize with staining for keratin 1, indicating that differentiated keratinocytes express NRP1. Similar to the expression of NRP1, VEGF-A was expressed in suprabasal epithelial cells, whereas Nrp2 and VEGFR2 were not detectable in the epidermis. The expression of NRP1 correlated with a high degree of differentiation in human SCC specimens, human SCC xenografts, and mouse K14-HPV16 transgenic SCC. UVB irradiation of mouse skin induced Nrp1 upregulation. In vitro, Nrp1 was upregulated in primary keratinocytes in response to differentiating media or epidermal growth factor-family growth factors. In conclusion, the expression of NRP1 is regulated in the skin and is selectively produced in differentiated epithelial cells. NRP1 may function as a reservoir to sequester VEGF ligand within the epithelial compartment, thereby modulating its bioactivity.

[Purpose]:Frozen gloves (FG) are effective in preventing docetaxel-induced nail toxicity (DNT), but uncomfortable. The preventive effect of FG for DNT was compared using a standard (−25 to −30°C) or more comfortable (−10 to −20°C) preparation. [Methods]:Breast cancer patients receiving docetaxel were eligible. Each patient wore an FG (prepared at −10 to −20°C for 90 min) for 60 min without replacement on the right hand. The left hand was protected by standard methods (FG prepared at −25 to −30°C overnight and worn for 90 min with replacement at 45 min). The primary endpoint was DNT occurrence at 5 months. Secondary endpoints included docetaxel exposure [cumulative dose and area under the blood concentration time curve (AUC)] until DNT occurrence and discomfort from FG. The pharmacokinetics of docetaxel was assessed. [Results]:From 23 patients enrolled between December 2006 and June 2010, seven who received docetaxel for less than 5 months were excluded from evaluation. The median accumulated docetaxel dose was 700 mg/m2 (340–1430 mg/m2). Within 5 months of FG use, none developed protocol-defined DNT in either hand. Two patients (13%) developed DNT at 7.2 and 7.3 months, respectively, both at −10 to −20°C. In the control hand (−25 to −30°C), discomfort occurred in 92% of the cycles, compared to 15% in the experimental hand (−10 to −20°C). Five patients (22%) experienced pain at −25 to −30°C, but none did at −10 to −20°C. The degree of docetaxel exposure was not related to DNT occurrence in our study. [Conclusion]:A convenient preparation of FG at −10 to −20°C is almost as effective as a standard preparation at −25 to −30°C, with significantly less discomfort.

Members of the DAZ (Deleted in AZoospermia) gene family are important players in the process of gametogenesis and their dysregulation accounts for 10% of human male infertility. Boule, the ancestor of the family, is mainly involved in male meiosis in most organisms. With the exception of Drosophila and C. elegans, nothing is known on the function of boule in non-vertebrate animals. In the present study, we report on three boule orthologues in the flatworm Macrostomum lignano. We demonstrate that macbol1 and macbol2 are expressed in testes whilst macbol3 is expressed in ovaries and developing eggs. Macbol1 RNAi blocked spermatocyte differentiation whereas macbol2 showed no effect upon RNAi treatment. Macbol3 RNAi resulted in aberrant egg maturation and led to female sterility. We further demonstrated the evolutionary functional conservation of macbol1 by introducing this gene into Drosophila bol(1) mutants. Macbol1 was able to rescue the progression of fly meiotic divisions. In summary, our findings provide evidence for an involvement of boule genes in male and female gamete development in one organism. Furthermore, boule gene function is shown here for the first time in a lophotrochozoan. Our results point to a more diverse functional assignment of boule genes. Therefore, a better understanding of boule function in flatworms can help to elucidate the molecular mechanisms of and concomitant infertility in higher organisms including humans. [KEYWORDS: Amino Acid Sequence, Animals, Azoospermia/genetics, Drosophila/genetics/metabolism, Drosophila Proteins/genetics, Female, Helminth Proteins/genetics/metabolism/ physiology, Male, Meiosis, Molecular Sequence Data, Oogenesis/genetics, Phylogeny, Spermatogenesis/genetics, Turbellaria/embryology/ genetics], Members of the DAZ (Deleted in AZoospermia) gene family are important players in the process of gametogenesis and their dysregulation accounts for 10% of human male infertility. Boule, the ancestor of the family, is mainly involved in male meiosis in most organisms. With the exception of Drosophila and C. elegans, nothing is known on the function of boule in non-vertebrate animals. In the present study, we report on three boule orthologues in the flatworm Macrostomum lignano. We demonstrate that macbol1 and macbol2 are expressed in testes whilst macbol3 is expressed in ovaries and developing eggs. Macbol1 RNAi blocked spermatocyte differentiation whereas macbol2 showed no effect upon RNAi treatment. Macbol3 RNAi resulted in aberrant egg maturation and led to female sterility. We further demonstrated the evolutionary functional conservation of macbol1 by introducing this gene into Drosophila bol(1) mutants. Macbol1 was able to rescue the progression of fly meiotic divisions. In summary, our findings provide evidence for an involvement of boule genes in male and female gamete development in one organism. Furthermore, boule gene function is shown here for the first time in a lophotrochozoan. Our results point to a more diverse functional assignment of boule genes. Therefore, a better understanding of boule function in flatworms can help to elucidate the molecular mechanisms of and concomitant infertility in higher organisms including humans. [KEYWORDS: Amino Acid Sequence, Animals, Azoospermia/genetics, Drosophila/genetics/metabolism, Drosophila Proteins/genetics, Female, Helminth Proteins/genetics/metabolism/ physiology, Male, Meiosis, Molecular Sequence Data, Oogenesis/genetics, Phylogeny, Spermatogenesis/genetics, Turbellaria/embryology/ genetics]

Members of the DAZ (Deleted in AZoospermia) gene family are important players in the process of gametogenesis and their dysregulation accounts for 10% of human male infertility. Boule, the ancestor of the family, is mainly involved in male meiosis in most organisms. With the exception of Drosophila and C. elegans, nothing is known on the function of boule in non-vertebrate animals. In the present study, we report on three boule orthologues in the flatworm Macrostomum lignano. We demonstrate that macbol1 and macbol2 are expressed in testes whilst macbol3 is expressed in ovaries and developing eggs. Macbol1 RNAi blocked spermatocyte differentiation whereas macbol2 showed no effect upon RNAi treatment. Macbol3 RNAi resulted in aberrant egg maturation and led to female sterility. We further demonstrated the evolutionary functional conservation of macbol1 by introducing this gene into Drosophila bol(1) mutants. Macbol1 was able to rescue the progression of fly meiotic divisions. In summary, our findings provide evidence for an involvement of boule genes in male and female gamete development in one organism. Furthermore, boule gene function is shown here for the first time in a lophotrochozoan. Our results point to a more diverse functional assignment of boule genes. Therefore, a better understanding of boule function in flatworms can help to elucidate the molecular mechanisms of and concomitant infertility in higher organisms including humans. [KEYWORDS: Amino Acid Sequence, Animals, Azoospermia/genetics, Drosophila/genetics/metabolism, Drosophila Proteins/genetics, Female, Helminth Proteins/genetics/metabolism/ physiology, Male, Meiosis, Molecular Sequence Data, Oogenesis/genetics, Phylogeny, Spermatogenesis/genetics, Turbellaria/embryology/ genetics], Members of the DAZ (Deleted in AZoospermia) gene family are important players in the process of gametogenesis and their dysregulation accounts for 10% of human male infertility. Boule, the ancestor of the family, is mainly involved in male meiosis in most organisms. With the exception of Drosophila and C. elegans, nothing is known on the function of boule in non-vertebrate animals. In the present study, we report on three boule orthologues in the flatworm Macrostomum lignano. We demonstrate that macbol1 and macbol2 are expressed in testes whilst macbol3 is expressed in ovaries and developing eggs. Macbol1 RNAi blocked spermatocyte differentiation whereas macbol2 showed no effect upon RNAi treatment. Macbol3 RNAi resulted in aberrant egg maturation and led to female sterility. We further demonstrated the evolutionary functional conservation of macbol1 by introducing this gene into Drosophila bol(1) mutants. Macbol1 was able to rescue the progression of fly meiotic divisions. In summary, our findings provide evidence for an involvement of boule genes in male and female gamete development in one organism. Furthermore, boule gene function is shown here for the first time in a lophotrochozoan. Our results point to a more diverse functional assignment of boule genes. Therefore, a better understanding of boule function in flatworms can help to elucidate the molecular mechanisms of and concomitant infertility in higher organisms including humans. [KEYWORDS: Amino Acid Sequence, Animals, Azoospermia/genetics, Drosophila/genetics/metabolism, Drosophila Proteins/genetics, Female, Helminth Proteins/genetics/metabolism/ physiology, Male, Meiosis, Molecular Sequence Data, Oogenesis/genetics, Phylogeny, Spermatogenesis/genetics, Turbellaria/embryology/ genetics]

This letter reports the control of the c-axis orientation and the magnetic properties of L10 FePd in the well-annealed FePd/Fe thin films Fe(20 nm)/FePd(10 nm)/Fe(5 nm)/SiO2-substrate and Fe(20 nm)/FePd(5 nm)/Fe(5 nm)/SiO2-substrate, with the compositions of dual phase region in phase equilibrium. After annealing at 550 °C for 24 h, the c-axis of L1[sub 0]FePd is controlled to be oriented in the normal direction in the soft Fe matrix. These thin films exhibit the exchange-coupling of hard FePd with soft Fe, and a characteristic spring-magnet behavior showed up reversibly as a significant jump from positive to negative in the magnetization reversal.

A Fulde-Ferrell-Larkin-Ovchinnkov (FFLO) state was previously reported in the quasi-2D heavy fermion CeCoIn5 when a magnetic field was applied parallel to the ab plane. Here, we conduct 115In NMR studies of this material in a perpendicular field, and provide strong evidence for FFLO in this case as well. Although the topology of the phase transition lines in the H-T phase diagram is identical for both configurations, there are several remarkable differences between them. Compared to H k ab, the FFLO phase for H ⊥ ab is confined in a much narrower region at the low-T–high-H corner in the H-T plane, and the critical field separating the FFLO and non-FFLO superconducting states almost ceases to have a temperature dependence. Moreover, directing H ⊥ ab results in a notable change in the quasiparticle excitation spectrum within the planar node associated with the FFLO transition.

A Fulde-Ferrell-Larkin-Ovchinnkov (FFLO) state was previously reported in the quasi-2D heavy fermion CeCoIn5 when a magnetic field was applied parallel to the ab plane. Here, we conduct 115In NMR studies of this material in a perpendicular field, and provide strong evidence for FFLO in this case as well. Although the topology of the phase transition lines in the H-T phase diagram is identical for both configurations, there are several remarkable differences between them. Compared to H k ab, the FFLO phase for H ⊥ ab is confined in a much narrower region at the low-T–high-H corner in the H-T plane, and the critical field separating the FFLO and non-FFLO superconducting states almost ceases to have a temperature dependence. Moreover, directing H ⊥ ab results in a notable change in the quasiparticle excitation spectrum within the planar node associated with the FFLO transition.