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In this audio essay, the author/speaker contemplates the perceived relationship between the voice and the speaker—the person in the voice—and asks the following questions: What does it mean when we...

Background and objectives Substance use behaviors have been identified as a risk factor that places juveniles at greater risk for engaging in delinquent behaviors and continual contact with the juvenile justice system. Currently, there is lack of research that explores comorbid factors associated with substance use, such as post-traumatic stress disorder (PTSD) symptoms, that could help identify youth who are at greatest risk. The aim of the present study was to examine if PTSD symptomology moderated the relationship between substance use disorder (SUD) symptoms and externalizing behaviors and commission of a violent crime; hypothesizing that risk would be heightened among youth with elevated SUD and PTSD symptomology compared to those with elevated SUD symptoms but lower PTSD symptoms. Method The study included 194 predominantly male (78.4%), non-White (74.2%) juvenile justice youth between the ages of 9-18 (M = 15.36). Youth provided responses to assess PTSD symptoms, SUD symptoms, and externalizing behaviors. Commission of a violent crime was based on parole officer report. Results Findings indicated that SUD symptomology was associated with greater externalizing behaviors at high levels of PTSD symptomology. At low levels of PTSD symptomology, SUD symptoms were inversely associated with externalizing behaviors. An interactive relationship was not observed for commission of violent crimes. Conclusions Findings suggest that the association between SUD symptoms and externalizing behaviors among juvenile offenders may be best explained by the presence of PTSD symptomology. Scientific significance Addressing PTSD rather than SUD symptoms may be a better target for reducing risk for externalizing behaviors among this population of youth (Am J Addict 2019;28:29-35).

Research shows that racial discrimination results in adverse behavioral health outcomes for African American young adults, including risk for depression, anxiety, and substance use. Although high levels of mindfulness have been shown to reduce risk for such health outcomes, it is unknown whether mindfulness can reduce risk as a consequence of racial discrimination, particularly among African Americans. Three-hundred and eighty-eight African American young adults between the ages of 18–24 (M=20.6, 62% female) completed measures assessing past year experiences of racial discrimination, depressive symptoms, anxiety symptoms, alcohol use, and trait mindfulness. A positive correlation was found between racial discrimination and the behavioral health outcomes, as well as a negative correlation between mindfulness and the behavioral health outcomes. Moreover, mindfulness was found to significantly moderate the effect of racial discrimination on mood symptoms. Although mindfulness was found to lessen the effect of racial discrimination on alcohol use, this difference was not statistically significant. In line with previous literature, racial discrimination was shown to have a negative impact on behavioral health outcomes among African Americans. Moreover, our findings provide support for the buffering effect of mindfulness on mood symptoms as a consequence discrimination. This suggests that increasing mindfulness may be an effective strategy to include in interventions targeting improvement in mood symptoms for African American young adults. However, alternative strategies may be more appropriate to address outcomes, such as alcohol use, as a consequence of racial discrimination.

BACKGROUND. Substance use behaviors have been identified as a risk factor that places juveniles at greater risk for engaging in delinquent behaviors and continual contact with the juvenile justice system. Currently, there is lack of research that explores comorbid factors associated with substance use, such as post-traumatic stress disorder (PTSD) symptoms, that could help identify youth who are at greatest risk. The aim of the present study was to examine if PTSD symptomology moderated the relationship between substance use disorder (SUD) symptoms and externalizing behaviors and commission of a violent crime; hypothesizing that risk would be heightened among youth with elevated SUD and PTSD symptomology compared to those with elevated SUD symptoms but lower PTSD symptoms. METHOD. The study included 194 predominantly male (78.4%), non-White (74.2%) juvenile justice youth between the ages of 9–18 (M=15.36). Youth provided responses to assess PTSD symptoms, SUD symptoms, and externalizing behaviors. Commission of a violent crime was based on parole officer report. RESULTS. Findings indicated that SUD symptomology was associated with greater externalizing behaviors at high levels of PTSD symptomology. At low levels of PTSD symptomology, SUD symptoms were inversely associated with externalizing behaviors. An interactive relationship was not observed for commission of violent crimes. DISCUSSION. Findings suggest that the association between SUD symptoms and externalizing behaviors among juvenile offenders may be best explained by the presence of PTSD symptomology. SCIENTIFIC SIGNIFICANCE. Addressing PTSD rather than SUD symptoms may be a better target for reducing risk for externalizing behaviors among this population of youth.

Objectives Racial discrimination is associated with numerous negative health outcomes, including increased risk for depression and anxiety symptoms and substance use. Positive affect toward of one's ethnic or racial group (i.e., ethnic-racial identity affirmation) has been shown to buffer the negative effects of racial discrimination on health outcomes. The extent to which one believes his or her group is valued by others (i.e., positive collective ethnic-racial identity) has also been proposed to be protective. However, to date a limited body of research has examined the moderating effect of collective ethnic-racial identity on health, and among available studies, findings are mixed. Method African American youth (N = 612; 58.2% female, M grade = 8) completed measures on experiences of discrimination, mood symptoms, substance use, ethnic-racial identity affirmation, and collective ethnic-racial identity (assessed using the Collective Self-Esteem Scale). Results Controlling for demographic variables and affirmation, a significant main effect was found for collective ethnic-racial identity, such that believing that others viewed your group positively was associated with better health outcomes among African American youth. However, collective ethnic-racial identity was not found to buffer the effects of discrimination on health outcomes. Conclusions These findings highlight the importance of examining collective ethnic-racial identity and the promotive effect it can have on health outcomes for African Americans. More research is needed to better understand if there are health outcomes in which collective ethnic-racial identity may also mitigate risk as a consequence of racial discrimination. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Outer membrane proteins (OMPs) in Gram-negative bacteria are essential for a number of cellular functions including nutrient transport and drug efflux. Escherichia coli BamA is an essential component of the OMP β-barrel assembly machinery and a potential novel antibacterial target that has been proposed to undergo large (~15 Å) conformational changes. Here, we explored methods to isolate anti-BamA monoclonal antibodies (mAbs) that might alter the function of this OMP and ultimately lead to bacterial growth inhibition. We first optimized traditional immunization approaches but failed to identify mAbs that altered cell growth after screening >3000 hybridomas. We then developed a “targeted boost-and-sort” strategy that combines bacterial cell immunizations, purified BamA protein boosts, and single hybridoma cell sorting using amphipol-reconstituted BamA antigen. This unique workflow improves the discovery efficiency of FACS + mAbs by >600-fold and enabled the identification of rare anti-BamA mAbs with bacterial growth inhibitory activity in the presence of a truncated lipopolysaccharide layer. These mAbs represent novel tools for dissecting the BamA-mediated mechanism of β-barrel folding and our workflow establishes a new template for the efficient discovery of novel mAbs against other highly dynamic membrane proteins.

The folding and insertion of integral β-barrel membrane proteins into the outer membrane of Gram-negative bacteria is required for viability and bacterial pathogenesis. Unfortunately, the lack of selective and potent modulators to dissect β-barrel folding in vivo has hampered our understanding of this fundamental biological process. Here, we characterize a monoclonal antibody that selectively inhibits an essential component of the

Huntington's disease is caused by expression of a mutant form of Huntingtin protein containing an expanded polyglutamine repeat. One possible treatment for Huntington's disease may be to reduce expression of mutant Huntingtin in the brain via RNA interference. Unless the therapeutic molecule is designed to be allele-specific, both wild-type and mutant protein will be suppressed by an RNA interference treatment. A key question is whether suppression of wild-type as well as mutant Huntingtin in targeted brain regions can be tolerated and result in a net benefit to patients with Huntington's disease. Whether Huntingtin performs essential functions in the adult brain is unclear. Here, we tested the hypothesis that the adult primate brain can tolerate moderately reduced levels of wild-type Huntingtin protein for an extended period of time. A serotype 2 adeno-associated viral vector encoding for a short hairpin RNA targeting rhesus huntingtin messenger RNA (active vector) was bilaterally injected into the striatum of four adult rhesus monkeys. Four additional animals received a comparable vector encoding a scrambled control short hairpin RNA (control vector). General health and motor behaviour were monitored for 6 months. Upon termination, brain tissues were sampled and assessed blindly for (i) huntingtin messenger RNA knockdown; (ii) Huntingtin protein expression; and (iii) neuropathological changes. Reduction in wild-type huntingtin messenger RNA levels averaging ∼30% was measured in the striatum of active vector recipients 6 months post-injection. A widespread reduction in Huntingtin protein levels was also observed by immunohistochemistry in these animals, with an average protein reduction of ∼45% relative to controls measured by western blot analysis in the putamen of active vector recipients. As with control vector recipients, no adverse effects were observed behaviourally, and no neurodegeneration was found on histological examination of active vector recipients. Our results suggest that long-term partial suppression of wild-type Huntingtin may be safe, and thus if a comparable level of suppression of mutant Huntingtin is beneficial, then partial suppression of both wild-type and mutant Huntingtin may result in a net benefit in patients with heterozygous Huntington's disease.

Multiple small-molecule inhibitors of the β-secretase enzyme (BACE1) are under preclinical or clinical investigation for Alzheimer's disease (AD). Prior work has illustrated robust lowering of central amyloid β (Aβ) after acute administration of BACE1 inhibitors. However, very few studies have assessed the overall impact of chronically administered BACE1 inhibitors on brain amyloid burden, neuropathology, and behavioral function in aged preclinical models. We investigated the effects of a potent nonbrain-penetrant BACE1 inhibitor, delivered directly to the brain using intracerebroventricular infusion in an aged transgenic mouse model. Intracerebroventricular infusion of the BACE1 inhibitor (0.3–23.5 μg/d) for 8 weeks, initiated in 17-month-old Tg2576 mice, produced dose-dependent increases in brain inhibitor concentrations (0.2–13 μm). BACE1 inhibition significantly reversed the behavioral deficit in contextual fear conditioning, and reduced brain Aβ levels, plaque burden, and associated pathology (e.g., dystrophic neurites), with maximal effects attained with ∼1 μg/d dose. Strikingly, the BACE1 inhibitor also reversed amyloid pathology below baseline levels (amyloid burden at the start of treatment), without adversely affecting cerebral amyloid angiopathy, microhemorrhages, myelination, or neuromuscular function. Inhibitor-mediated decline in brain amyloid pathology was associated with an increase in microglial ramification. This is the first demonstration of chronically administered BACE1 inhibitor to activate microglia, reverse brain amyloid pathology, and elicit functional improvement in an aged transgenic mouse model. Thus, engagement of novel glial-mediated clearance mechanisms may drive disease-modifying therapeutic benefit with BACE1 inhibition in AD.

Using the Career Key as a criterion measure, the validity of the Strong Interest Explorer was tested with a sample of Latino junior high school and senior high school students. A total of 85 Hispanic youth were administered the Strong Interest Explorer and the Career Key in counterbalanced order. Separate correlational analyses were conducted for (a) the total sample, (b) junior high/senior high students, and (c) males/females. Results generally offered support for the validity of the Strong Interest Explorer Artistic, Social and Enterprising scales but not the Investigative, Conventional or Realistic scales. Cautions regarding use of the Strong Interest Explorer with Latino youth are discussed. ********** Latinos are the largest minority group in the United States. According to the 2000 Census, there are 35.3 million Latinos living in the U. S. It is expected that by 2050, Latinos will represent approximately 25 percent of the total U.S. population. Latinos are also one of the youngest population groups in the United States. One-third of Latinos are under 18 years of age, and they represent approximately 15 percent of the K-12 population (2002 National Directory, 2002). Furthermore, between the years 2000 and 2025, the U.S. Census Bureau projects that the number of working-age Latino Americans will increase by 18 million. However, only 57 percent of Latinos 25 years and older have completed high school. Twenty-seven percent of Latinos have less than a high school education. College-qualified Latino students are the only racial/ethnic group significantly less likely than other college-qualified students to pursue post-secondary education (2002 National Directory, 2002). According to the National Educational Longitudinal Survey (NELS), only 55% of Latino eighth graders expect to get college degrees (Our Nation on the Fault Line, 1996). Latino youth continue to be underrepresented in higher education. According to the 2000 Census, only 10.6 percent of Hispanics have attained a bachelor's degree. In 1996, Latinos represented only 4 percent of students in graduate school and approximately 8 percent of first-year professional students. Latino American high school graduates still trail other population groups in attaining college degrees, according to a report recently released by the Pew Hispanic Center (PHC) (Fry, 2002). Only 35% of Latino high school graduates 18 to 24 years old are enrolled in college compared to 46% of whites. The Baccalaureate degree completion rate for Latinos is currently at 10%. This combines to produce the lowest completion rates and highest dropout rates for the fastest growing minority group in the US (McGlynn, 2001). Latinos also tend to be over-represented in occupational categories such as farming, labor, factory-type work, and service industry occupations. Only 28% of males of Latino descent hold upper-level managerial, technical, and administrative positions, compared to 48% of nonLatino males. As the level of education or skill increases for a particular job, the percentage of Latinos in that position diminishes (U.S. Bureau of the Census, 1988). Under-representation of Latino workers is especially severe in high-tech jobs that require college or graduate degrees, due to unequal access to the types of postsecondary education required for science and technology jobs. Only 1.3% of Latinos had college-educated technical jobs. Latinos are also underrepresented in education, health care, management, accounting, sales, and marketing (Our Nation on the Fault Line, 1996). Similarly, Latinos remain severely underrepresented in science and engineering education, and male Latinos are disproportionately represented among the lower levels of employment in manufacturing. In academic settings, Latinos represented only 2.7% of doctoral science and engineering faculty in 1995 (Muller-Karger, 2000). Clearly, such dismal statistics offer strong evidence that this population of students is in dire need of career development services and career planning assistance. …

We evaluated relationships between climatological variables and abundance of larval yellow perch (Perca flavescens) in eastern South Dakota glacial lakes. Age-0 yellow perch were collected using a 0.75 m diameter ichthyoplankton net from May through mid-June at 7 to 10 d intervals. Highest correlation coefficients with larval yellow perch abundance were for April total precipitation (r-0.95–0.99; P=0.09–0.01; three lakes), mean March wind speed (r=-0.98 to −0.99; P=0.02–0.006; two lakes), mean of May average daily temperatures (1-0.78; P=0.12; one lake) and mean May wind speed (r=-0.82; P=0.02; one lake). Given the low number of years in some samples, individual years at times had undue influence on the relationship, resulting in high correlation coefficients. Multiple regression modeling resulted in improved models for only two of the seven lakes (R2=0.90–0.98; P=0.05–0.02). However, March through May weather patterns in some combination were related to larval yellow perch abundance in all seven...

Retroviral Gag proteins perform important functions in viral assembly, but are also involved in other steps in the viral life cycle. Conventional mutational analysis has yielded considerable information about domains essential for these functions, yet many regions of gag remain uncharacterized. We used genetic footprinting, a technique that permits the generation and simultaneous analysis of large numbers of mutations, to perform a near-saturation mutagenesis and functional analysis of 639 nucleotides in the gag region of Moloney murine leukemia virus. We report here the resulting functional map defined by eight footprints representing regions of Moloney murine leukemia virus gag , some previously uncharacterized, that are essential for replication. We found that significant portions of matrix and p12 proteins were tolerant of insertions, in contrast to the N-terminal half of capsid, which was not. We analyzed 30 mutants from our library by using conventional methods to validate the footprints. Six of these mutants were characterized in detail, identifying the precise stage at which their replication is blocked. In addition to providing the most comprehensive functional map of a retroviral gag gene, our study demonstrates the abundance of information that can be gleaned by genetic footprinting of viral sequences.

Alewives were collected by nighttime gill netting during summer 1999 from 12 Connecticut lakes that support landlocked populations to determine relationships between population characteristics and physicochemical lake variables. Mean catch-per-unit-effort (CPUE) ranged from 0.2 to 16.4 age-1 and older alewives per net hour. Maximum ages of alewives among lakes ranged from two to five years, and mean back-calculated length-at-age-1, used to index growth rate, ranged from 78 to 146 mm. Mean back-calculated length-at-age-1 was positively correlated with mean relative condition factor (Kn), watershed area:lake surface area ratio, watershed area:lake volume ratio, lake surface area:lake volume ratio, conductivity, total nitrogen, alkalinity, calcium, magnesium, and chlorophyll a, and negatively correlated with retention time, maximum lake depth, mean lake depth, and transparency. Mean Kn ranged from 0.93 to 1.23 and was positively correlated with mean back-calculated length-at-age-1, watershed area:la...

Human cytomegalovirus (HCMV) is the most common cause of congenital virus infection. Congenital HCMV infection occurs in 0.2–1% of all births, and causes birth defects and developmental abnormalities, including sensorineural hearing loss and developmental delay. Several key studies have established the guinea pig as a tractable model for the study of congenital HCMV infection and have shown that polyclonal antibodies can be protective [1]–[3]. In this study, we demonstrate that an anti-guinea pig CMV (GPCMV) glycoprotein H/glycoprotein L neutralizing monoclonal antibody protects against fetal infection and loss in the guinea pig. Furthermore, we have delineated the kinetics of GPCMV congenital infection, from maternal infection (salivary glands, seroconversion, placenta) to fetal infection (fetus and amniotic fluid). Our studies support the hypothesis that a neutralizing monoclonal antibody targeting an envelope GPCMV glycoprotein can protect the fetus from infection and may shed light on the therapeutic intervention of HCMV congenital infection in humans., Author Summary Human cytomegalovirus (HCMV) is the most common cause of congenital virus infection and causes developmental abnormalities, including hearing loss and developmental delay. Although there is no therapy for congenital HCMV disease, there is evidence from both human and animal studies that antibodies can have efficacy in this setting. Such studies have focused exclusively on polyclonal antibodies, in which the targets of protective antibodies are unknown. Guinea pigs have been used as a model of human maternal fetal transmission of infection because of similarities in placental anatomy between human and guinea pig. Furthermore, guinea pig CMV (GPCMV) has been demonstrated to cross the placenta and cause fetal infection and loss, similar to the effects of infection with HCMV. However, the kinetics of maternal and fetal infection in this model has not been carefully investigated. In this work, we have delineated the kinetics of maternal to fetal infection and found that congenital infection is rapid following maternal infection. Importantly, we demonstrate that a monoclonal antibody against a protein critical for viral entry protects pregnant guinea pigs against fetal infection. Thus, our studies may be informative for development of a therapeutic intervention to treat congenital HCMV infection in humans.

During summer 1999, 5,004 landlocked alewives (Alosa pseudoharengus) were captured from 12 Connecticut lakes using horizontal gill nets with mesh sizes of 9.5, 12.7, 15.9, 19.1, 25.4, and 31.8 mm (bar measure). The most effective mesh size was 12.7-mm, capturing 3,035 alewives. The modal length of alewives caught in each mesh size increased as the mesh size increased from 9.5 to 25.4 mm. No alewives less than 70 mm total length or greater than 245 mm were captured. Modal lengths of selectivity curves estimated indirectly using the Holt model were 85, 114, 143, 172, and 228 mm for the 9.5-, 12.7–15.9-, 19. 1-, and 25.4-mm mesh sizes, respectively. Adding a 22.3-mm mesh and removing the 31.8-mm mesh is suggested to sample landlocked alewives between 100 and 245 mm in Connecticut lakes.

The primary sequence of the long unique region L-DNA (L for low GC) of rhesus monkey rhadinovirus (RRV) isolate 26-95 was determined. The L-DNA consists of 130,733 bp that contain 84 open reading frames (ORFs). The overall organization of the RRV26-95 genome was found to be very similar to that of human Kaposi sarcoma-associated herpesvirus (KSHV). BLAST search analysis revealed that in almost all cases RRV26-95 coding sequences have a greater degree of similarity to corresponding KSHV sequences than to other herpesviruses. All of the ORFs present in KSHV have at least one homologue in RRV26-95 except K3 and K5 (bovine herpesvirus-4 immediate-early protein homologues), K7 (nut-1), and K12 (Kaposin). RRV26-95 contains one MIP-1 and eight interferon regulatory factor (vIRF) homologues compared to three MIP-1 and four vIRF homologues in KSHV. All homologues are correspondingly located in KSHV and RRV with the exception of dihydrofolate reductase (DHFR). DHFR is correspondingly located near the left end of the genome in RRV26-95 and herpesvirus saimiri (HVS), but in KSHV the DHFR gene is displaced 16,069 nucleotides in a rightward direction in the genome. DHFR is also unusual in that the RRV26-95 DHFR more closely resembles HVS DHFR (74% similarity) than KSHV DHFR (55% similarity). Of the 84 ORFs in RRV26-95, 83 contain sequences similar to the recently determined sequences of the independent RRV isolate 17577. RRV26-95 and RRV17577 sequences differ in that ORF 67.5 sequences contained in RRV26-95 were not found in RRV17577. In addition, ORF 4 is significantly shorter in RRV26-95 than was reported for RRV17577 (395 versus 645 amino acids). Only four of the corresponding ORFs between RRV26-95 and RRV17577 exhibited less than 95% sequence identity: glycoproteins H and L, uracil DNA glucosidase, and a tegument protein (ORF 67). Both RRV26-95 and RRV17577 have unique ORFs between positions 21444 to 21752 and 110910 to 114899 in a rightward direction and from positions 116524 to 111082 in a leftward direction that are not found in KSHV. Our analysis indicates that RRV26-95 and RRV17577 are clearly independent isolates of the same virus species and that both are closely related in structural organization and overall sequence to KSHV. The availability of detailed sequence information, the ability to grow RRV lytically in cell culture, and the ability to infect monkeys experimentally with RRV will facilitate the construction of mutant strains of virus for evaluating the contribution of individual genes to biological properties.

All members of the Herpesviridae family contain sequences for a highly conserved glycoprotein B (gB) gene. We investigated the phylogenetic relationships of gB sequences from eight independent rhadinovirus isolates obtained from three species: rhesus ( Macaca mulatta ), cynomologus ( Macaca fasicularis ), and pig-tailed ( Macaca nemestrina ) macaques. Samples were derived from monkeys housed at four separate facilities. Analysis of these eight independent gB sequences revealed five regions of heterogeneity within the 823- to 829-amino-acid polypeptides: residues 1 to 65, 120 to 185, 255 to 300, 352 to 393, and 412 to 457. The remaining regions of gB were highly conserved among the different macaque isolates. Overall divergence among these gene sequences ranged from 0.1 to 7.2% at the amino acid level. Phylogenetic trees constructed with our macaque rhadinovirus gB sequences and those derived from additional subfamilies or genera (alpha, beta, gamma-1, and gamma-2) revealed that the macaque gB sequences branched with other gamma-2 herpesvirus gB sequences and that within the gamma-2 genera, the macaque gB sequences clustered as a distinct branch. The eight macaque rhadinovirus gB sequences were all approximately equidistant from Kaposi sarcoma-associated herpesvirus (KSHV) gB sequences and had a shorter evolutionary distance to KSHV gB sequences than to any other herpesvirus, including the gamma-2 herpesvirus saimiri (HVS) of New World squirrel monkeys. The macaque gB sequences did not cluster according to the facility of origin, but did cluster according to the species of origin, displaying less intraspecies divergence (0.1 to 2.9%) than interspecies divergence (3.3 to 7.2%). These results demonstrate a close relatedness of rhadinovirus isolates from different macaque species.