University of Medicine and Dentistry of New Jersey

About: University of Medicine and Dentistry of New Jersey is a based out in . It is known for research contribution in the topics: Population & Pregnancy. The organization has 14634 authors who have published 19610 publications receiving 1041794 citations.

Mutations in ANKH Cause Chondrocalcinosis

Abstract: Chondrocalcinosis (CC) is a common cause of joint pain and arthritis that is caused by the deposition of calcium-containing crystals within articular cartilage. Although most cases are sporadic, rare familial forms have been linked to human chromosomes 8 (CCAL1) or 5p (CCAL2) (Baldwin et al. 1995; Hughes et al. 1995; Andrew et al. 1999). Here, we show that two previously described families with CCAL2 have mutations in the human homolog of the mouse progressive ankylosis gene (ANKH). One of the human mutations results in the substitution of a highly conserved amino acid residue within a predicted transmembrane segment. The other creates a new ATG start site that adds four additional residues to the ANKH protein. Both mutations segregate completely with disease status and are not found in control subjects. In addition, 1 of 95 U.K. patients with sporadic CC showed a deletion of a single codon in the ANKH gene. The same change was found in a sister who had bilateral knee replacement for osteoarthritis. Each of the three human mutations was reconstructed in a full-length ANK expression construct previously shown to regulate pyrophosphate levels in cultured cells in vitro. All three of the human mutations showed significantly more activity than a previously described nonsense mutation that causes severe hydroxyapatite mineral deposition and widespread joint ankylosis in mice. These results suggest that small sequence changes in ANKH are one cause of CC and joint disease in humans. Increased ANK activity may explain the different types of crystals commonly deposited in human CCAL2 families and mutant mice and may provide a useful pharmacological target for treating some forms of human CC.

A short leader sequence impairs the fidelity of initiation by eukaryotic ribosomes

Abstract: The functional consequences of unusually short 5' noncoding sequences on eukaryotic mRNAs are explored here by using an in vitro transcription and translation system As the distance of the first AUG codon from the m7G cap was decreased from 32 to 3 nucleotides, the yield of protein initiated from the first AUG codon progressively decreased, with a corresponding increase in initiation from the second AUG codon The leakiness attributable to a too-short leader sequence was offset, however, by introducing secondary structure downstream from the first AUG codon

The Utility of the Ces-D as a Depression Screening Measure among Low-Income Women Attending Primary Care Clinics

Abstract: Objective:Depressive disorders are among the most common medical disorders seen in primary care practice. The Center for Epidemiologic Studies-Depression (CES-D) scale is one of the measures commonly suggested for detecting depression in these clinics. However, to our knowledge, there have been no previous studies examining the validity of the CES-D among low-income women attending primary care clinics.Method:Low-income women attending public primary care clinics (n = 179, ages 20–77) completed the CES-D and the Diagnostic Interview Schedule for the DSM-IV (DIS-IV).Results:The results supported the validity of the CES-D. The standard cut-score of 16 and above yielded a sensitivity of .95 and specificity of .70 in predicting Major Depressive Disorder (MDD). However, over two-thirds of those who screened positive did not meet criteria for MDD (positive predictive value = .28). The standard cut-score appears valid, but inefficient for depression screening in this population. An elevated cut-score of 34 yield...

Evidence of cis -acting factors in replication-mediated trinucleotide repeat instability in primate cells

Abstract: The mechanism of disease-associated trinucleotide repeat instability involves cis-acting factors (cis-elements) in the vicinity of the repeat, but the nature of these elements is unknown. One cis-element may be the location of the replication origin relative to the repeat. We have used an SV40 DNA replication system to investigate the effect of the location of replication initiation on (CTG)(n)*(CAG)(n) stability in primate cells. Depending on the distance between the SV40 replication origin and the repeat tract, templates with 79 repeats yield predominantly expansions or predominantly deletions or remain intact. All templates with 17 repeats are stable. Thus, cis-elements that affect the sites of Okazaki fragment initiation relative to the repeat are crucial determinants of instability. This model system recapitulates the bias for expansions observed in many of the diseases associated with trinucleotide repeats. Our results might explain the variable amounts of CTG/CAG instability that are observed in different chromosomal contexts.