Posttraumatic Stress Disorder Symptoms,Intimate Partner Violence,and Relationship Functioning: A Meta‐Analytic Review

This meta‐analysis was the first study of which we are aware to investigate the association between Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM‐IV‐TR; American Psychiatric Association, 2000) PTSD symptom clusters and parent, child, family, and marital/partner functioning problems (e.g., intimate partner violence [IPV] and intimacy). Of the 23 studies that met inclusion criteria, the sample was predominantly male (83.8%), Caucasian (65.0%), and from the military (98.9%). The average age was 43.65 years old (SD = 6.27); the average sample size was 397.4 (SD = 416.9; total N = 9,935). PTSD symptom clusters were assessed primarily by self‐report (87.0%), with 8.7% using a rating by a clinician. We used fixed analysis following Fisher's r to z transformation and an unbiased weighing and summing of effect sizes within samples and across studies. We found a small association between hyperarousal and IPV (z = .20). We also found two moderate associations for the emotional numbing and avoidance symptom clusters: (a) with parent, child, and family functioning (z = .32, z = .28, respectively); and (b) with intimacy problems (z = .35, z = .42, respectively). We found two large associations for emotional numbing: marital and parent problems (z = .47) and parent, child, and family functioning problems (z = .32, respectively). Our findings suggested that treatments aim to lessen the effect on those who have close relationships with the individual with PTSD.     

Identification and characterization of recombinant plasmids carrying the complete qa gene cluster from Neurospora crassa including the qa-1+ regulatory gene.

The early reactions in the catabolism of quinic acid in Neurospora crassa are controlled by at least four genes which are clustered on linkage group VII. Three of the loci (qa-2, qa-4, and qa-3) encode enzymes that convert quinic acid to protocatechuic acid. The fourth gene (qa-1) encodes a positive regulatory protein which, in the presence of quinic acid, leads to the de novo synthesis of the other proteins in the qa cluster. This communication describes a series of recombinant plasmids that span 36.5 kilobases of linkage group VII and contain the coding sequences for qa-2, qa-4, qa-3, and the qa-1 regulatory protein. The plasmids were obtained by partial digestion of wild-type N. crassa DNA with EcoRI and ligation into the cosmid cloning vehicle pHC79. Two independently derived plasmids (pMSK331 and pMSK335), each containing 36.5-kilobase inserts, were shown by transformation back into N. crassa to contain the entire qa gene cluster. A preliminary physical organization of the gene cluster is presented. An improved procedure for the transformation of N. crassa with plasmid DNA is also described.     

Multiple-dose, safety, pharmacokinetics, and pharmacodynamics of a new selective estrogen receptor modulator, ERA-923, in healthy postmenopausal women

ERA-923 is a new selective estrogen receptor modulator under clinical investigation for use in tamoxifen refractory metastatic breast cancer. This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of once-daily oral ERA-923 (10-200 mg) for 28 days in healthy postmenopausal females. ERA-923 was well tolerated, and adverse events were mild and reversible. No clinically significant changes in laboratory values were found with ERA-923 versus placebo. ERA-923 appeared to undergo extensive metabolism and enterohepatic recirculation. In addition, pharmacokinetic analysis showed that a high-fat breakfast increased the extent of absorption. ERA-923-dosed subjects had no uterine or ovarian changes when evaluated with transvaginal ultrasound and compared to placebo subjects. Overall, ERA-923 was safe and well tolerated in postmenopausal women dosed for 28 days.     

Role of cytoplasmic dynein in perinuclear aggregation of phagocytosed melanosomes and supranuclear melanin cap formation in human keratinocytes

Cytoplasmic dynein is a microtubule-associated motor molecule involved in the retrograde transport of membrane-bound organelles. To determine whether the supranuclear melanin cap of transferred, phagocytosed melanosomes in keratinocytes is associated with cytoplasmic dynein, we performed immunofluorescent confocal microscopy on human keratinocytes in situ. We identified the intermediate chain of cytoplasmic dynein by immunoblotting and examined its distribution by confocal microscopy in relation to microtubules and melano-phagolysosomes in vitro. We also used antisense and sense oligonucleotides of the cytoplasmic dynein heavy chain 1 (Dyh1) and time-lapse and microscopy. The intermediate chain of cytoplasmic dynein was identified in extracts of human foreskin epidermis and in isolated human keratinocytes. The intermediate chain localized with the perinuclear melano-phagolysosomal aggregates in vitro and the supranuclear melanin cap in situ. Antisense oligonucleotides directed towards Dyh1 resulted in dispersal of the keratinocyte perinuclear melano-phagolysosomal aggregates after 24 to 48 h, whereas cells treated with diluent or sense oligonucleotides maintained tight perinuclear aggregates. Taken together, these findings indicate that in human keratinocytes, the retrograde microtubule motor cytoplasmic dynein mediates the perinuclear aggregation of phagocytosed melanosomes, participates in the formation of the supranuclear melanin cap or "microparasol" and serves as a mechanism to help protect the nucleus from ultraviolet-induced DNA damage.