Mice with mutations in Mahogunin ring finger-1 (Mgrn1) exhibit abnormal patterning of the left-right axis.

Mahogunin Ring Finger 1 (Mgrn1) encodes a RING-containing protein with ubiquitin ligase activity that has been implicated in pigment-type switching. In addition to having dark fur, mice lacking MGRN1 develop adult-onset spongy degeneration of the central nervous system and have reduced embryonic viability. Observation of complete situs inversus in a small proportion of adult Mgrn1 mutant mice suggested that embryonic lethality resulted from congenital heart defects due to defective establishment and/or maintenance of the left-right (LR) axis. Here we report that Mgrn1 is expressed in a pattern consistent with a role in LR patterning during early development and that many Mgrn1 mutant embryos show abnormal expression of asymmetrically expressed genes involved in LR patterning. A range of complex heart defects was observed in 20-25% of mid-to-late gestation Mgrn1 mutant embryos and another 20% were dead. This finding was consistent with 46-60% mortality of mutants by weaning age. Our results indicate that Mgrn1 acts early in the LR signaling cascade and is likely to provide new insight into this developmental process as Nodal expression was uncoupled from expression of other Nodal-responsive genes in Mgrn1 mutant embryos. Our work identifies a novel role for MGRN1 in embryonic patterning and suggests that the ubiquitination of MGRN1 target genes is essential for the proper establishment and/or maintenance of the LR axis.     

Heterogeneous pattern of chromosomal breakpoints involving the MYC locus in multiple myeloma

Chromosomal rearrangements of the MYC locus, which often involve the IG loci, are recurrent events in multiple myeloma (MM) and plasma cell leukemia (PCL). We used dual-color fluorescence in situ hybridization (FISH) to characterize the breakpoint locations of chromosomal translocations/rearrangements involving the MYC locus at 8q24 found in a panel of 14 MM cell lines and 70 primary tumors (66 MM and 4 PCL). MYC locus alterations were observed in 21 cases: MYC/IG (mainly IGH@) fusions in 11 cell lines and three patients (2 MM and 1 PCL), and extra signals and/or abnormal MYC localizations in seven patients (5 MM and 2 PCL). Fourteen of these cases were investigated by FISH analyses by use of a panel of BAC clones covering about 6 Mb encompassing the MYC locus. The breakpoints were localized in a region 100-250 kb centromeric to MYC in four cases, a region 500-800 kb telomeric to the gene in four cases, and regions > or = 2 Mb centromeric or telomeric to MYC in five cases. Two different breakpoints were detected in the KMS-18 cell line, whereas the insertion of a MYC allele was found in a complex t(16;22) chromosomal translocation in the RPMI8226 cell line. Our data document a relatively high dispersion of 8q24 breakpoints in MM.     

The N-terminal domain of the vaccinia virus E3L-protein is required for neurovirulence, but not induction of a protective immune response

Encephalitis is a rare, but serious complication from vaccination against smallpox using replication competent strains of vaccinia virus. In this report we describe mutants of vaccinia virus, containing N-terminal deletions of the vaccinia virus interferon resistance gene, E3L, that are attenuated for neuropathogenesis in a mouse model system. These recombinant viruses replicated to high titers in the nasal mucosa after intra-nasal infection of C57BL/6 mice but failed to spread to the lungs or brain. These viruses demonstrated reduced pathogenicity after intra-cranial infection as well, indicating a decrease in neurovirulence. Intra-nasal inoculation or inoculation by scarification with a low dose of recombinant virus containing a deletion of the entire N-terminal domain of E3L protected against challenge with a high dose of wild-type vaccinia virus, suggesting that this replication competent, but attenuated strain of vaccinia virus may have promise as an improved vaccine for protecting against smallpox, and as a vector for inducing mucosal immunity to heterologous pathogenic organisms.     

Identification of 26 new constitutional RB1 gene mutations in Spanish, Colombian, and Cuban retinoblastoma patients

Constitutional mutations in the RB1 gene predispose to retinoblastoma development. Hence genetic screening of retinoblastoma patients and relatives is important for genetic counseling purposes. In addition, RB1 gene mutation studies may help decipher the molecular mechanisms leading to tumors with different degrees of penetrance or expressivity. In the course of genetically screening of 107 hereditary and non-hereditary retinoblastoma patients (11 familiar bilateral, 4 familiar unilateral, 49 sporadic bilateral and 43 sporadic unilateral) and kindred from Spain, Colombia and Cuba, using direct PCR sequencing, we observed 45 distinct mutations and four RB1 deletions in 53 patients (9 familiar bilateral, 2 familiar unilateral, 31 sporadic bilateral and 11 sporadic unilateral). Most of these mutations (26/45, 57%) have not been reported before. In 32 patients, the predisposing mutations correspond to nonsense (mainly CpG transitions) and small insertions or deletions whose expected outcome is a truncated Rb protein that lacks the functional pockets and tail. Five single aminoacid replacements and seventeen mutations affecting splicing sites were also observed in retinoblastoma patients. Two of these sixteen mutations are of unclear pathogenic nature.     

Investigation of Gamma-aminobutyric acid (GABA) A receptors genes and migraine susceptibility

Background  

Migraine is a neurological disorder characterized by recurrent attacks of severe headache, affecting around 12% of Caucasian populations. It is well known that migraine has a strong genetic component, although the number and type of genes involved is still unclear. Prior linkage studies have reported mapping of a migraine gene to chromosome Xq 24–28, a region containing a cluster of genes for GABA A receptors (GABRE, GABRA3, GABRQ), which are potential candidate genes for migraine. The GABA neurotransmitter has been implicated in migraine pathophysiology previously; however its exact role has not yet been established, although GABA receptors agonists have been the target of therapeutic developments. The aim of the present research is to investigate the role of the potential candidate genes reported on chromosome Xq 24–28 region in migraine susceptibility. In this study, we have focused on the subunit GABA A receptors type ε (GABRE) and type θ (GABRQ) genes and their involvement in migraine.     

Complex Acetylenes from the Roots of Ferula communis

The benzene extract from the roots of FERULA COMMUNIS afforded the coumarin ferulenol ( 1) and the structurally related acetylenes named ferulinolone [3-(1,2-dihydrofalcarinolonyl)-ferulenol] ( 4) and decarboxyferulinolone [2-nor-3-(1,2-dihydrofal-carinolonyl-ferulenol] ( 7). The structures of these substances were deduced from their spectral data and those of their derivatives, mainly from the (1)H- and (13)C-NMR 1D and 2D spectra (one bond and long-range correlations). Methoxylatifolone ( 10) was also isolated from this extract.     

Establishing the minimal clinically important difference of the EQ-5D-3L in older adults with a history of falls

Quality of Life Research - Establish the minimal clinically important difference (MCID) of a health-related quality of life (HRQoL) measure—the EuroQol EQ-5 Dimensions-3 Level...     

Improving Postpartum Care: Identifying Opportunities to Reduce Postpartum Emergency Room Visits Among Publicly-Insured Women of Color

Maternal and Child Health Journal - The purpose of this study was to explore the postpartum experiences of publicly-insured women of color, and identify how postpartum care can be improved to...     

Asking About Childhood Adversity in the Prenatal Care Setting: Cross-Sectional Associations with Maternal Health and Mental Health Outcomes

Maternal and Child Health Journal - Adverse childhood experiences (ACEs) are associated with poor physical and mental health outcomes in pregnancy, prompting many care agencies to ask about ACEs as...     

Musculoskeletal injury survivors’ resiliency: A systematic review

BackgroundMusculoskeletal traumas are on the rise in the United States; however, limited studies are available to help trauma providers assess and treat concerns beyond the physical impact. Little is understood about the psychological, social, and spiritual factors that protect patients from adverse effects after a physical trauma or their experiences with each factor afterward.ObjectiveThis systematic review was conducted to investigate and review advancements in research related to risk and resiliency factors experienced by survivors of traumatic musculoskeletal injuries. The use of biopsychosocial-spiritual (BPS–S) framework and resiliency theory guided the analysis.MethodsResearchers reviewed 1003 articles, but only seven met the search criteria. Due to the complexity and uniqueness of traumatic brain injuries, studies on that target population were excluded.ResultsOf the seven articles reviewed, three identified psychological protective factors that protect against negative health outcomes; three identified negative psychological, social, or spiritual outcomes; and none investigated social or spiritual health.ConclusionsThere are significant gaps in the literature surrounding risk and resiliency factors related to the BPS-S health of musculoskeletal injury survivors.