Requirement of Mouse BCCIP for Neural Development and Progenitor Proliferation

Multiple DNA repair pathways are involved in the orderly development of neural systems at distinct stages. The homologous recombination (HR) pathway is required to resolve stalled replication forks and critical for the proliferation of progenitor cells during neural development. BCCIP is a BRCA2 and CDKN1A interacting protein implicated in HR and inhibition of DNA replication stress. In this study, we determined the role of BCCIP in neural development using a conditional BCCIP knock-down mouse model. BCCIP deficiency impaired embryonic and postnatal neural development, causing severe ataxia, cerebral and cerebellar defects, and microcephaly. These development defects are associated with spontaneous DNA damage and subsequent cell death in the proliferative cell populations of the neural system during embryogenesis. With in vitro neural spheroid cultures, BCCIP deficiency impaired neural progenitor's self-renewal capability, and spontaneously activated p53. These data suggest that BCCIP and its anti-replication stress functions are essential for normal neural development by maintaining an orderly proliferation of neural progenitors

Two-dimensional amine and hydroxy functionalized fused aromatic covalent organic framework

Ordered two-dimensional covalent organic frameworks (COFs) have generally been synthesized using reversible reactions. It has been difficult to synthesize a similar degree of ordered COFs using irreversible reactions. Developing COFs with a fused aromatic ring system via an irreversible reaction is highly desirable but has remained a significant challenge. Here we demonstrate a COF that can be synthesized from organic building blocks via irreversible condensation (aromatization). The as-synthesized robust fused aromatic COF (F-COF) exhibits high crystallinity. Its lattice structure is characterized by scanning tunneling microscopy and X-ray diffraction pattern. Because of its fused aromatic ring system, the F-COF structure possesses high physiochemical stability, due to the absence of hydrolysable weak covalent bonds

Congenital bronchial atresia presenting as a cavitary lesion on chest radiography: a case report

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Ezrin, a membrane cytoskeleton cross-linker protein, as a marker of epithelial damage in asthma

RATIONALE: Bronchial epithelial cell damage occurs in patients with bronchial asthma. Ezrin, a membrane-cytoskeleton protein, maintains cellular morphology and intercellular adhesion and protects the barrier function of epithelial cells. OBJECTIVES: To study the role of ezrin in bronchial epithelial cells injury and correlate its expression with asthma severity. METHODS: Levels of ezrin were measured in exhaled breath condensate (EBC) and serum in asthma patients and bronchoalveolar lavage fluid (BALF) from a mouse model of asthma by ELISA. The regulation of IL-13 on ezrin protein levels was studied in primary bronchial epithelial cells (PBECs). Ezrin knockdown using shRNA was studied in human bronchial epithelial 16HBE cells. RESULTS: Ezrin levels were decreased in asthmatic EBC (392.7±34.99 vs 150.5±10.22 pg/ml, p<0.0001) and serum (700.7±55.59 vs 279.2±25.83pg/ml, p<0.0001) compared to normal subjects. Levels were much lower in uncontrolled (p<0.001) and partly-controlled patients (p<0.01) compared to well-controlled subjects. EBC and serum ezrin levels correlated with lung function in asthma patients and serum ezrin levels were negatively correlated with serum IL-13 and periostin. IL-13-induced down-regulation of ezrin expression in PBECs was significantly attenuated by the JAK2 (Janus tyrosine kinase 2) inhibitor TG101348. Ezrin knockdown changed 16HBE cell morphology, enlarged intercellular spaces and increased their permeability. Ezrin expression was decreased in the lung tissue and BALF of 'asthmatic' mice and negatively correlated with BALF IL-13 level. CONCLUSIONS: Ezrin down-regulation is associated with IL-13-induced epithelial damage and might be a potential biomarker of asthma control

SALL4 Expression in Gonocytes and Spermatogonial Clones of Postnatal Mouse Testes

The spermatogenic lineage is established after birth when gonocytes migrate to the basement membrane of seminiferous tubules and give rise to spermatogonial stem cells (SSC). In adults, SSCs reside within the population of undifferentiated spermatogonia (Aundiff) that expands clonally from single cells (Asingle) to form pairs (Apaired) and chains of 4, 8 and 16 Aaligned spermatogonia. Although stem cell activity is thought to reside in the population of Asingle spermatogonia, new research suggests that clone size alone does not define the stem cell pool. The mechanisms that regulate self-renewal and differentiation fate decisions are poorly understood due to limited availability of experimental tools that distinguish the products of those fate decisions. The pluripotency factor SALL4 (sal-like protein 4) is implicated in stem cell maintenance and patterning in many organs during embryonic development, but expression becomes restricted to the gonads after birth. We analyzed the expression of SALL4 in the mouse testis during the first weeks after birth and in adult seminiferous tubules. In newborn mice, the isoform SALL4B is expressed in quiescent gonocytes at postnatal day 0 (PND0) and SALL4A is upregulated at PND7 when gonocytes have colonized the basement membrane and given rise to spermatogonia. During steady-state spermatogenesis in adult testes, SALL4 expression overlapped substantially with PLZF and LIN28 in Asingle, Apaired and Aaligned spermatogonia and therefore appears to be a marker of undifferentiated spermatogonia in mice. In contrast, co-expression of SALL4 with GFRα1 and cKIT identified distinct subpopulations of Aundiff in all clone sizes that might provide clues about SSC regulation. Collectively, these results indicate that 1) SALL4 isoforms are differentially expressed at the initiation of spermatogenesis, 2) SALL4 is expressed in undifferentiated spermatogonia in adult testes and 3) SALL4 co-staining with GFRα1 and cKIT reveals distinct subpopulations of Aundiff spermatogonia that merit further investigation. © 2013 Gassei, Orwig

Cerebellopontine epidermoid presenting with trigeminal neuralgia for 10 years: a case report

Trigeminal neuralgia, also called tic douloureux, is a common and potentially disabling pain syndrome, which affects the trigeminal or fifth cranial nerve. The precise pathophysiology of Trigeminal neuralgia remains obscure. The disorder causes extreme, sporadic, sudden burning or shock-like face pain that lasts from few seconds to minutes and can be physically and mentally incapacitating. More than one nerve branch can be affected by the disorder. A 55-year-old female presented with pain over the left side of face for 10 years uncontrolled with carbamazepine. On examination the positive findings were reduced sensation by 25% over the left side of face with House and Brackman grade II facial nerve palsy. The corneal reflex was absent on left side. Magnetic resonance imaging showed left cerebellopontine angle (CPA) mass suggestive of an epidermoid involving the Vth nerve and Gasserian ganglion and extending into the middle cranial fossa. She underwent left suboccipital craniectomy and near total excision of the tumor with decompression of the Vth nerve which was fully engulfed by the tumor. Postoperative the VII nerve palsy increased to grade III and she had 50% loss of sensation over left side. She had no further attacks of pain and hence tapered off the carbamazepine. TN caused by cerebellopontine angle epidermoids is uncommon and should be kept in view in all cases presenting with TN. The aim of surgery for epidermoids is to decompress the cranial nerves and brain stem and not total removal with its attendant morbidity and mortality

Essential Roles of BCCIP in Mouse Embryonic Development and Structural Stability of Chromosomes

BCCIP is a BRCA2- and CDKN1A(p21)-interacting protein that has been implicated in the maintenance of genomic integrity. To understand the in vivo functions of BCCIP, we generated a conditional BCCIP knockdown transgenic mouse model using Cre-LoxP mediated RNA interference. The BCCIP knockdown embryos displayed impaired cellular proliferation and apoptosis at day E7.5. Consistent with these results, the in vitro proliferation of blastocysts and mouse embryonic fibroblasts (MEFs) of BCCIP knockdown mice were impaired considerably. The BCCIP deficient mouse embryos die before E11.5 day. Deletion of the p53 gene could not rescue the embryonic lethality due to BCCIP deficiency, but partially rescues the growth delay of mouse embryonic fibroblasts in vitro. To further understand the cause of development and proliferation defects in BCCIP-deficient mice, MEFs were subjected to chromosome stability analysis. The BCCIP-deficient MEFs displayed significant spontaneous chromosome structural alterations associated with replication stress, including a 3.5-fold induction of chromatid breaks. Remarkably, the BCCIP-deficient MEFs had a ∼20-fold increase in sister chromatid union (SCU), yet the induction of sister chromatid exchanges (SCE) was modestly at 1.5 fold. SCU is a unique type of chromatid aberration that may give rise to chromatin bridges between daughter nuclei in anaphase. In addition, the BCCIP-deficient MEFs have reduced repair of irradiation-induced DNA damage and reductions of Rad51 protein and nuclear foci. Our data suggest a unique function of BCCIP, not only in repair of DNA damage, but also in resolving stalled replication forks and prevention of replication stress. In addition, BCCIP deficiency causes excessive spontaneous chromatin bridges via the formation of SCU, which can subsequently impair chromosome segregations in mitosis and cell division

Complete chloroplast genome sequence of Holoparasite Cistanche Deserticola (Orobanchaceae) reveals gene loss and horizontal gene transfer from Its host Haloxylon Ammodendron (Chenopodiaceae)

The central function of chloroplasts is to carry out photosynthesis, and its gene content and structure are highly conserved across land plants. Parasitic plants, which have reduced photosynthetic ability, suffer gene losses from the chloroplast (cp) genome accompanied by the relaxation of selective constraints. Compared with the rapid rise in the number of cp genome sequences of photosynthetic organisms, there are limited data sets from parasitic plants. The authors report the complete sequence of the cp genome of Cistanche deserticola, a holoparasitic desert species belonging to the family Orobanchaceae