Environmental influences on human innovation and behavioural diversity in southern Africa 92-80 thousand years ago.

Africa's Middle Stone Age preserves sporadic evidence for novel behaviours among early modern humans, prompting a range of questions about the influence of social and environmental factors on patterns of human behavioural evolution. Here we document a suite of novel adaptations dating approximately 92-80 thousand years before the present at the archaeological site Varsche Rivier 003 (VR003), located in southern Africa's arid Succulent Karoo biome. Distinctive innovations include the production of ostrich eggshell artefacts, long-distance transportation of marine molluscs and systematic use of heat shatter in stone tool production, none of which occur in coeval assemblages at sites in more humid, well-studied regions immediately to the south. The appearance of these novelties at VR003 corresponds with a period of reduced regional wind strength and enhanced summer rainfall, and all of them disappear with increasing winter rainfall dominance after 80 thousand years before the present, following which a pattern of technological similarity emerges at sites throughout the broader region. The results indicate complex and environmentally contingent processes of innovation and cultural transmission in southern Africa during the Middle Stone Age.

ALD1613, a Novel Long-Acting Monoclonal Antibody to Control ACTH-Driven Pharmacology.

Adrenocorticotropic hormone (ACTH) is the primary regulator of adrenal glucocorticoid production. Elevated levels of ACTH play a critical role in disease progression in several indications, including congenital adrenal hyperplasia and Cushing disease. We have generated a specific, high-affinity, neutralizing monoclonal antibody (ALD1613) to ACTH. In vitro, ALD1613 neutralizes ACTH-induced signaling via all 5 melanocortin receptors and inhibited ACTH-induced cyclic adenosine monophosphate accumulation in a mouse adrenal cell line (Y1). ALD1613 administration to wild-type rats significantly reduced plasma corticosterone levels in a dose-dependent manner. In rodent models with either chronic infusion of ACTH or acute restraint stress-induced ACTH, corticosterone levels were significantly reduced by ALD1613. Administration of ALD1613 to nonhuman primates on days 1 and 7 stably reduced plasma cortisol levels >50% for 57 days. ALD1613 demonstrates the potential of a monoclonal antibody to be an effective therapeutic for conditions with elevated ACTH levels.

The process and promise of mental health augmentation of nurse home-visiting programs: Data from the Louisiana Nurse-Family Partnership.

The Nurse-Family Partnership (NFP) model is a well-studied and effective preventive intervention program targeting first-time, impoverished mothers and their families. Data documenting the negative impact of maternal depression and partner violence on the developing young child can be used to make a strong case for augmenting NFP programs to focus on mental health problems impacting the mother-child relationship. This article reviews the rationale for and process of augmenting an NFP program in Louisiana. Data on the prevalence of depression and partner violence in our sample are presented alongside a training protocol for nurses and mental health consultants designed to increase the focus on infant mental health. The use of a weekly case conference and telephone supervision of mental health consultants as well as reflections on the roles of the mental health consultant and the nurse supervisor are presented.

Characterization of KLK4 expression and detection of KLK4-specific antibody in prostate cancer patient sera.

The ability to identify prostate tumor or prostate tissue specific genes that are expressed at high levels and use their protein products as targets could greatly aid in the diagnosis and treatment of prostate cancer. Using a polymerase chain reaction (PCR)-based subtraction technique, we have recovered the recently described KLK4 (prostase) gene from human prostate cDNA. In this study, KLK4 gene expression in human prostate tumors was further characterized using cDNA quantitative PCR and immunohistochemistry, demonstrating that the gene is specifically expressed at both the mRNA and protein levels in normal human prostate tissue, and in both primary and metastatic prostate tumor samples. Quantitative mRNA analysis also demonstrated low level expression including adrenal gland, salivary gland and thyroid. Finally, it was demonstrated that prostate cancer patient sera contain antibodies that bind specifically to recombinant KLK4 protein. This antibody has been used to detect KLK4-specific peptides in epitope mapping experiments. The relatively specific expression profile and elevated level of KLK4 mRNA and protein in both tumor and normal prostate tissues, in addition to detectable KLK4-specific antibody in cancer patient sera, supports additional efforts to determine if KLK4 can play a role in the diagnosis of prostate cancer, the monitoring of residual disease, or act as a target for immunotherapy.

Serum antibodies to lipophilin B detected in late stage breast cancer patients.

Lipophilin B mRNA is overexpressed in approximately 70% of breast tumors and shows a high degree of correlation with the mRNA expression profile of mammaglobin. This is further supported by the recent finding that, like other members of the secretoglobulin-uteroglobin family, mammaglobin and lipophilin B form a heteroduplex. The studies described show that there are pre-existing antibodies to lipophilin B peptide in the sera of breast cancer patients with different stages and grade of tumor and that this response is different from that seen to recombinant mammaglobin and native mammaglobin-lipophilin B complex. The highest titers were observed in later stage tumors. In addition, low levels of antibody were also seen in some patients with prostate and ovarian cancers, consistent with lipophilin B mRNA expression in these tumors at lower abundance than in breast tumors. In contrast, lipophilin B antibodies were absent in 20 healthy donor sera and 30 lung cancer sera. A polymorphism identified in Lipophilin B did not appear to influence human sera reactivity. The data indicate that humoral immune responses to lipophilin B may serve as a diagnostic indicator, particularly for breast cancer.

VSGP/F-spondin: a new ovarian cancer marker.

The discovery of genes that are overexpressed in ovarian cancers provides valuable insight into ovarian cancer biology and will lead to the development of more effective treatment strategies for combating this disease. To identify genes exhibiting ovarian- and ovarian cancer-specific expression, we generated four subtracted cDNA libraries from primary and metastatic ovarian adenocarcinoma tissues. 3,400 cDNA clones from these libraries were analyzed by microarray for tissue distribution and tumor specificity using 32 pairs of fluorophore-labeled cDNA samples from a variety of normal tissues and ovarian tumor tissues. cDNA clones showing elevated expression in ovarian tumors were identified by DNA sequencing with comparison to public databases, and the most promising candidates were further analyzed by quantitative real-time polymerase chain reaction and Northern blot. This systematic approach led to the identification of a number of genes including vascular smooth muscle growth-promoting factor (VSGP/F-spondin), a secreted protein previously identified and cloned from bovine and human ovary. VSGP/F-spondin protein was observed in ovarian carcinomas but not in normal ovarian epithelium by immunohistochemistry with a VSGP/F-spondin antibody. The expression profile of VSGP/F-spondin identifies this molecule as a potential diagnostic marker or target for developing therapeutic strategies to treat ovarian carcinoma.

Identification and characterization of putative secreted antigens from Babesia microti.

The need for improved diagnostic reagents to identify human long-term carriers of the zoonotic parasite Babesia microti is evidenced by numerous reported cases of transfusion-acquired infections. This report describes the identification and initial characterization of 27 clones representing seven genes or gene families that were isolated through serological expression cloning by using a technique that we specifically designed to screen for shed antigens. In this screen, sera from B. microti-infected SCID mice, putatively containing secreted or shed antigens from the parasites, were harvested and used to immunize syngeneic immunocompetent mice (BALB/c). After boosting, the sera from the BALB/c mice, containing antibodies against the immunodominant secreted antigens, were used to screen a B. microti genomic expression library. Analyses of the putative peptides encoded by the novel DNA sequences revealed characteristics indicating that these peptides might be secreted. Initial serological data obtained with recombinant proteins and a patient serum panel demonstrated that several of the proteins could be useful in developing diagnostic tests for detection of B. microti antibodies and antigens in serum.

Use of multiepitope polyproteins in serodiagnosis of active tuberculosis.

Screening of genomic expression libraries from Mycobacterium tuberculosis with sera from tuberculosis (TB) patients or rabbit antiserum to M. tuberculosis led to the identification of novel antigens capable of detecting specific antibodies to M. tuberculosis. Three antigens, Mtb11 (also known as CFP-10), Mtb8, and Mtb48, were tested together with the previously reported 38-kDa protein, in an enzyme-linked immunosorbent assay (ELISA) to detect antibodies in TB patients. These four proteins were also produced as a genetically fused polyprotein, which was tested with two additional antigens, DPEP (also known as MPT32) and Mtb81. Sera from individuals with pulmonary and extrapulmonary TB, human immunodeficiency virus (HIV)-TB coinfections, and purified protein derivative (PPD)-positive and PPD-negative status with no evidence of disease were tested. In samples from HIV-negative individuals, the ELISA detected antibodies in >80% of smear-positive individuals and >60% smear-negative individuals, with a specificity of approximately 98%. For this group, smears detected 81.6% but a combination of smear and ELISA had a sensitivity of approximately 93%. The antigen combination detected a significant number of HIV-TB coinfections as well as antibodies in patients with extrapulmonary infections. Improved reactivity in the HIV-TB group was observed by including the antigen Mtb81 that was identified by proteomics. The data indicate that the use of multiple antigens, some of which are in a single polyprotein, can be used to facilitate the development of a highly sensitive test for M. tuberculosis antibody detection.