Do age- and sex-related variations reliably reflect body size in non-human primate vocalizations? A review

In vocal communication, the mechanisms of sound production are well understood. The length of the vocal folds determines the minimum fundamental frequency, while the size and the shape of the vocal tract affect its filtering characteristics and hence, the resonant frequencies. Both measures-vocal fold length and vocal tract length-are related to body size and therefore, acoustic features are expected to vary with body size. Because direct measures of body size are difficult to obtain from free-ranging animals, age and sex have often been used as proxies. We surveyed studies which included direct measures of size or weight, and also studies in which only age and/or sex differences were examined. The main purpose was to examine whether age- and sex-related variations in acoustic features meet the predictions generated from our knowledge about sound production. Our survey revealed that compared to smaller animals, larger animals utter longer calls, with a lower fundamental frequency, with smaller formant dispersion, and with the energy concentrated in lower frequencies. Age and sex reliably reflect the influence of body size on acoustic features when gross size differences are examined. However, within age- and sex classes, this relationship may break down. In addition to body size, other factors such as internal state or social context may also influence the structure of vocal signals and highlight the richness of information in calls that is potentially available to listeners.     

Health Facility Utilisation Changes during the Introduction of Community Case Management of Malaria in South Western Uganda: An Interrupted Time Series Approach

Background

Malaria endemic countries have scaled-up community health worker (CHW) interventions, to diagnose and treat malaria in communities with limited access to public health systems. The evaluations of these programmes have centred on CHW’s compliance to guidelines, but the broader changes at public health centres including utilisation and diagnoses made, has received limited attention.

Methods

This analysis was conducted during a CHW–intervention for malaria in Rukungiri District, Western Uganda. Outpatient department (OPD) visit data were collected for children under-5 attending three health centres one year before the CHW-intervention started (pre-intervention period) and for 20 months during the intervention (intervention-period). An interrupted time series analysis with segmented regression models was used to compare the trends in malaria, non-malaria and overall OPD visits during the pre-intervention and intervention-period.

Results

The introduction of a CHW-intervention suggested the frequency of diagnoses of diarrhoeal diseases, pneumonia and helminths increased, whilst the frequency of malaria diagnoses declined at health centres. In May 2010 when the intervention began, overall health centre utilisation decreased by 63% compared to the pre-intervention period and the health centres saw 32 fewer overall visits per month compared to the pre-intervention period (p<0.001). Malaria visits also declined shortly after the intervention began and there were 27 fewer visits per month during the intervention-period compared with the pre-intervention period (p<0.05). The declines in overall and malaria visits were sustained for the entire intervention-period. In contrast, there were no observable changes in trends of non-malarial visits between the pre-intervention and intervention-period.

Conclusions

This analysis suggests introducing a CHW-intervention can reduce the number of child malaria visits and change the profile of cases presenting at health centres. The reduction in workload of health workers may allow them to spend more time with patients or undertake additional curative or preventative roles.     

Wild Female Olive Baboons Adapt their Grunt Vocalizations to Environmental Conditions

Sound propagates differently and visibility varies according to the habitat type. Animals should therefore adapt the acoustic structure and the usage of their vocal signals to the environment. In the present study, we examined the influence of the habitat on the vocal behaviour of wild olive baboons ( Papio hamadryas anubis ) in two populations: one living in Gashaka-Gumti National Park, Nigeria, and the other in Budongo Forest, Uganda. We investigated whether female baboons modified the acoustic structure of their grunts and their rate of grunting when they wandered between closed and open habitat types. As an adaptation to the environmental conditions, baboons might utter calls with a longer duration, a lower fundamental frequency and/or energy concentrated in lower frequencies in a closed habitat like forest than in an open habitat. Baboons should also grunt more frequently in the closed habitat. Analyses showed that in both populations grunts uttered in forest were significantly longer than in open habitat. Additionally, baboons from Uganda showed a significantly higher grunt rate in forest than in open habitat. These results revealed a certain degree of plasticity in vocal production and call usage with regard to the habitat type. However, results in Nigeria suggested that, besides habitat structure, other proximate factors like the context of calling and the proximity between group members could also have an influence on the actual communication patterns.     

Circadian rhythm in airway responsiveness and airway tone in patients with mild asthma.

To determine the characteristics and reproducibility of circadian rhythms of airway responsiveness to histamine and methacholine and their relationship to airway tone in patients with mild asthma, we studied nine subjects with complaints of nighttime awakening due to dyspnea and/or cough at least once a week. Their mean age was 31.4 yr (range 17-65) and their mean daytime FEV1 was 99 +/- 14 (SD) % predicted. Forced expiratory volume in 1 s (FEV1) and the provocative concentrations of histamine and methacholine necessary to decrease FEV1 by 20% (PC20FEV1) were determined every 4 h for 13 consecutive measurements. Three subjects were measured with histamine, three with methacholine, and three with both histamine and methacholine. Data were evaluated on an individual basis. PC20FEV1 to histamine and methacholine showed significant and reproducible circadian variations in all cases (P less than 0.01 each) with a mean amplitude of 1.00 +/- 0.17 (SD) doubling concentrations for histamine and 1.35 +/- 0.29 doubling concentrations for methacholine. The amplitude of PC20FEV1 was significantly larger (P less than 0.05) and the time of maximum responsiveness was significantly earlier (P less than 0.05) with methacholine compared with histamine. FEV1 showed significant (P less than 0.05) circadian variations in three of nine subjects, and peak expiratory flow rate showed variations in two subjects. Correlation between the variations of FEV1 and PC20FEV1 was significant (P less than 0.05) in 5 of 12 cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Isolation and characterization of an antigen from the fish pathogen Moritella viscosa

Aims: Moritella viscosa is a Gram‐negative psychrophilic bacterium that causes winter ulcer disease in farmed fish. The aim of the study was to describe an outer membrane protein of roughly 20 kDa in pathogenic M. viscosa and to compare the coincident protein of strains isolated from different fish species and geographical locations. Methods and Results: The protein was isolated from a pathogenic strain of M. viscosa. An oligopeptide sequence obtained with MS/MS analysis showed homology to Escherichia coli OmpA and Neisseria surface protein A. The protein was named Moritella viscosa outer membrane protein 1 (MvOmp1), and sequence analysis confirmed that it is an integral membrane protein consisting of eight antiparallel β‐strands, three short periplasmic turns and four long hydrophilic extracellular loops. The encoding gene, mvomp1, was fully sequenced in nine strains representing different serotypes and phenotypes. The results revealed some differences in the extracellular loops between strains. The mvomp1 gene was cloned and expressed in E. coli, and the recombinant product was recognized by anti‐M. viscosa polyclonal antisera. Conclusions: The results indicate that MvOmp1 is a major protective antigen of M. viscosa. Significance and Impact of the Study: The results open up possibilities for use of the protein as a part of a subunit vaccine in the future.     

TLR2 Mediates Gap Junctional Intercellular Communication through Connexin-43 in Intestinal Epithelial Barrier Injury

Gap junctional intercellular communication (GJIC) coordinates cellular functions essential for sustaining tissue homeostasis; yet its regulation in the intestine is not well understood. Here, we identify a novel physiological link between Toll-like receptor (TLR) 2 and GJIC through modulation of Connexin-43 (Cx43) during acute and chronic inflammatory injury of the intestinal epithelial cell (IEC) barrier. Data from in vitro studies reveal that TLR2 activation modulates Cx43 synthesis and increases GJIC via Cx43 during IEC injury. The ulcerative colitis-associated TLR2-R753Q mutant targets Cx43 for increased proteasomal degradation, impairing TLR2-mediated GJIC during intestinal epithelial wounding. In vivo studies using mucosal RNA interference show that TLR2-mediated mucosal healing depends functionally on intestinal epithelial Cx43 during acute inflammatory stress-induced damage. Mice deficient in TLR2 exhibit IEC-specific alterations in Cx43, whereas administration of a TLR2 agonist protects GJIC by blocking accumulation of Cx43 and its hyperphosphorylation at Ser³⁶⁸ to prevent spontaneous chronic colitis in MDR1α-deficient mice. Finally, adding the TLR2 agonist to three-dimensional intestinal mucosa-like cultures of human biopsies preserves intestinal epithelial Cx43 integrity and polarization ex vivo. In conclusion, Cx43 plays an important role in innate immune control of commensal-mediated intestinal epithelial wound repair.The intestinal epithelial cell (IEC)³ barrier provides the front line of mucosal host defense in the intestine. The IEC barrier confers anatomic integrity and immunologic protection of the intestinal mucosal surface. Because the IEC barrier constantly faces diverse populations of lumenal microbes and other potential threats, it must exert a highly defined process of continuous discrimination: excluding harmful antigens while allowing host-beneficial substances to permeate (1, 2). Para- and intercellular transit of molecules is modulated by a complex network of closely arranged tight (TJ) and gap junctions (GJ) between juxtaposed IEC. Gap junctional intercellular communication (GJIC) is an essential, but not well understood, mechanism for cellular and tissue homeostasis that coordinates cell-cell passage of ions and small metabolites (<1 kDa). Thus, GJIC regulates cell proliferation, migration, and differentiation (3). GJ channels are formed by hexameric connexins at the plasma membrane. Cx43 is the major connexin and represents a key target in GJIC regulation (4). It is differentially phosphorylated at a dozen or more residues throughout its life cycle (5–9). Alteration of GJIC caused by changes in Cx43 has been proposed to be involved in the pathophysiology of diverse IEC barrier diseases, including inflammatory bowel diseases, necrotizing enterocolitis, cancer, and enteric infection (10–12). However, immune mediators that allow protective GJIC via Cx43 to sustain IEC barrier function during mucosal damage have not yet been identified.Toll-like receptor 2 (TLR2), a member of the TLR family that is constitutively expressed in IEC (13–15), recognizes conserved molecular patterns associated with both Gram-negative and -positive bacteria (16). We have previously shown that commensal-mediated TLR2 helps to maintain functional TJ barrier integrity of the intestinal epithelial layer. TLR2 enhances transepithelial resistance of the IEC barrier by apical redistribution of ZO-1 via protein kinase Cα/δ (17). Treatment with the TLR2 ligand PCSK protects ZO-1-associated IEC barrier integrity and decreases intestinal permeability in acute colitis (18). Previous studies in other cell types have demonstrated that the second PDZ domain of ZO-1 interacts with the carboxyl terminus of Cx43 (19, 20). ZO-1 binds to Cx43 preferentially during the G₀ phase, enhancing assembly and stabilization of GJIC (21, 22). Like TLR2, Cx43 and ZO-1 reside in caveolin-1-associated lipid raft microdomains (23–25). We therefore hypothesized that the binding between ZO-1 and Cx43 may allow TLR2 to control IEC barrier function by GJIC.In this study, we identified a new physiological mechanism of innate immune host defense in the injured intestine. Our findings indicated that Cx43 serves as an important component of the protective innate immune response of the intestinal epithelium. TLR2-induced GJIC via Cx43 appears to control IEC barrier function and restitution during acute and chronic inflammatory damage, enhancing mucosal homeostasis between commensals and host. UC-associated TLR2 mutant results in impaired GJIC by a proteasomal-dependent increase in Cx43 turnover.     

Synthetic retinoid CD437 induces apoptosis and acts synergistically with TRAIL receptor-2 agonist in malignant melanoma

The novel synthetic retinoid, CD437, shows potent anti-tumor activity in a range of different cancer cell lines and now serves as a prototype for development of new retinoid related molecules (RRMs). The purpose of this study was to examine the effect and cellular targets of CD437 in the human metastatic melanoma cell lines FEMX-1 and WM239. We showed that treatment with CD437 led to cell cycle arrest and induced apoptosis through both the extrinsic- and intrinsic pathways (caspase 8, -9 and PARP cleavage) in both cell lines. Interestingly, apoptosis was induced independently of DNA-fragmentation in FEMX-1 cells, and appeared partially caspase-independent in the WM239 cells. Additionally, up-regulation of CHOP mRNA and cathepsin D protein expression, following retinoid treatment, suggests involvement of the endoplasmatic reticulum (ER) and lysosomes, respectively. Combination of suboptimal concentrations of CD437 and lexatumumab, a TRAIL death receptor-2 agonist, resulted in synergistic reduction of viable cells, along with increased PARP cleavage. These results indicate that CD437 has a strong anti-neoplastic effect alone and in combination with lexatumumab in melanoma cell lines.     

Schistosomiasis-related perceptions, attitudes and treatment-seeking practices in Magu district, Tanzania: public health implications

A study on perceptions, attitudes and treatment-seeking practices related to schistosomiasis was conducted among the Wasukuma in the rural Magu district of Tanzania at the shore of Lake Victoria where Schistosoma haematobium and mansoni infections are endemic. The study applied in-depth interviews, focus group discussions and a questionnaire survey among adults and primary school children. The perceived symptoms and causes were incongruous with the biomedical perspective and a number of respondents found schistosomiasis to be a shameful disease. Lack of diagnostic and curative services at the government health care facilities was common, but there was a willingness from the biomedical health care services to collaborate with the traditional healers. Recommendations to the District Health Management Team were: that collaboration between biomedical and traditional health care providers should be strengthened and that the government facilities' diagnostic and curative capacity with regard to schistosomiasis should be upgraded. Culturally compatible health education programmes should be developed in collaboration with the local community.     

Giardia intestinalis:Conservation of the Variant-Specific Surface Protein VSP417-1 (TSA417) and Identification of a Divergent Homologue Encoded at a Duplicated Locus in Genetic Group II Isolates

Ey, P. L., and Darby, J. M. 1998.Giardia intestinalis: Conservation of the variant-specific surface protein VSP417-1 (TSA417) and identification of a divergent homologue encoded at a duplicated locus in genetic Group II isolates.Experimental Parasitology90, 250–261. The stability of the gene encoding TSA417, a 72-kDa variant-specific surface protein (VSP) produced by trophozoites ofGiardia intestinalisisolate WB-C6, was investigated in isolates of similar (Assemblage A / Group I) or distinct (Assemblage A / Group II) genotype. Using primers specific for the WB-C6tsa417gene, DNA amplified in polymerase chain reactions from genomic DNA indicated the presence, in every isolate, of an intact coding sequence possessing conserved restriction sites diagnostic for this locus (herein designatedvsp417-1). Sequence analysis of the DNA amplified from the genomes of genetic Group I (“A-I”) isolates revealed complete identity with the published WB-C6tsa417(vsp417-1^A-I) sequence. Equivalent products, amplified from the genomes of genetic Group II (“A-II”) isolates, similarly yielded an invariant and apparently allelic 2142-bp coding sequence (designatedvsp417-1^A-II) possessing 79% nucleotide identity withvsp417-1^A-Iand polymorphisms unique to Group II organisms. The encoded polypeptides (VSP417-1^A-Iand VSP417-1^A-II) are identical at 75% of amino acid positions. Substitutions are concentrated within the N-terminal portions of the proteins, but the overall structure of VSP417-1 has changed little during the evolution of the Group I and Group II genotypes from their common clonal ancestor. An additional 0.7-kb DNA, representing a separate locus (vsp417-5) encoding a 22.3-kDa VSP, was amplified from genetic Group II genomes exclusively but only using particular primer combinations. Thevsp417-5^A-IIgene exhibits >85% sequence identity with the 5′ and 3′ segments ofvsp417-1^A-Iandvsp417-1^A-IIbut it lacks a 1482-bp segment that comprises the central portion of thevsp417-1 locus. Excision of this segment seems to have occurred by intragenic recombination, possibly initiated by a stem loop formed between palindromic sequences which border the 1482-bp segment withinvsp417-1 but which are contiguous invsp417-5^A-II. The detection by Southern hybridization of additional genomic sequences that share homology with these genes reveals the existence in these two genotypes of a distinctive “vsp417” gene subset.     

A distribution model for heritability.

A regression model to predict quantiles of narrow sense individual and family mean heritabilities is developed and used to predict confidence intervals either directly or via a generalized beta distribution model. Extensive simulations of balanced sib analysis trials in randomized complete block designs and normal distributed environmental and additive genetic effects confirmed that heritabilities follow a beta distribution even in cases with up to 10% of the data missing at random. The new model is both more accurate and more precise than commonly used alternatives based on "exact" chi 2 distributions and Satterthwaites approximations to the degrees of freedom. Estimates of the expected heritability and a Taylor approximation of the standard error of the heritability are needed as input to the quantile model. Applications of the presented models for estimating confidence intervals and as an aid in the design of experiments are provided.