The ecological integrity of the lower Olifants River,Limpopo province,South Africa: 2009–2015 – Part B: Tributaries of the Olifants River

Monitoring on the Lowveld reaches of the Olifants River, Limpopo River System, and its Steelpoort, Blyde, Klaserie and Selati tributaries was initiated in 2009. Analysis of the 2009–2015 data from four Olifants River sites showed deterioration in the river’s ecological condition between where it enters the Lowveld and where it enters the Kruger National Park, with a slight recovery within the Kruger National Park. Physico-chemical, aquatic macroinvertebrate and fish data collected in 2009–2015 at six sites on the Steelpoort, Blyde, Klaserie and Selati tributaries of the Olifants River corroborated the ecological condition of these tributaries. The Selati was the most polluted and was in a critically modified condition, whereas the Klaserie and Steelpoort were in fair condition and the Blyde was in good condition. The Selati appeared to have a significant negative impact on the water quality, macroinvertebrates and fish of the Olifants River within the Kruger National Park.     

Pre- and Postnatal Nutritional Histories Influence Reproductive Maturation and Ovarian Function in the Rat

Background

While prepubertal nutritional influences appear to play a role in sexual maturation, there is a need to clarify the potential contributions of maternal and childhood influences in setting the tempo of reproductive maturation. In the present study we employed an established model of nutritional programming to evaluate the relative influences of prenatal and postnatal nutrition on growth and ovarian function in female offspring.

Methods

Pregnant Wistar rats were fed either a calorie-restricted diet, a high fat diet, or a control diet during pregnancy and/or lactation. Offspring then were fed either a control or a high fat diet from the time of weaning to adulthood. Pubertal age was monitored and blood samples collected in adulthood for endocrine analyses.

Results

We report that in the female rat, pubertal timing and subsequent ovarian function is influenced by the animal''s nutritional status in utero, with both maternal caloric restriction and maternal high fat nutrition resulting in early pubertal onset. Depending on the offspring''s nutritional history during the prenatal and lactational periods, subsequent nutrition and body weight gain did not further influence offspring reproductive tempo, which was dominated by the effect of prenatal nutrition. Whereas maternal calorie restriction leads to early pubertal onset, it also leads to a reduction in adult progesterone levels later in life. In contrast, we found that maternal high fat feeding which also induces early maturation in offspring was associated with elevated progesterone concentrations.

Conclusions

These observations are suggestive of two distinct developmental pathways leading to the acceleration of pubertal timing but with different consequences for ovarian function. We suggest different adaptive explanations for these pathways and for their relationship to altered metabolic homeostasis.     

Empirical Study of Data Sharing by Authors Publishing in PLoS Journals

Background

Many journals now require authors share their data with other investigators, either by depositing the data in a public repository or making it freely available upon request. These policies are explicit, but remain largely untested. We sought to determine how well authors comply with such policies by requesting data from authors who had published in one of two journals with clear data sharing policies.

Methods and Findings

We requested data from ten investigators who had published in either PLoS Medicine or PLoS Clinical Trials. All responses were carefully documented. In the event that we were refused data, we reminded authors of the journal''s data sharing guidelines. If we did not receive a response to our initial request, a second request was made. Following the ten requests for raw data, three investigators did not respond, four authors responded and refused to share their data, two email addresses were no longer valid, and one author requested further details. A reminder of PLoS''s explicit requirement that authors share data did not change the reply from the four authors who initially refused. Only one author sent an original data set.

Conclusions

We received only one of ten raw data sets requested. This suggests that journal policies requiring data sharing do not lead to authors making their data sets available to independent investigators.     

Immunobiological Outcomes of Repeated Chlamydial Infection from Two Models of Within-Host Population Dynamics

Background

Chlamydia trachomatis is a common human pathogen that mediates disease processes capable of inflicting serious complications on reproduction. Aggressive inflammatory immune responses are thought to not only direct a person''s level of immunity but also the potential for immunopathology. With human immunobiology being debated as a cause of prevailing epidemiological trends, we examined some fundamental issues regarding susceptibility to multiple chlamydial infections that could have implications for infection spread. We argue that, compared to less-frequent exposure, frequent exposure to chlamydia may well produce unique immunobiological characteristics that likely to have important clinical and epidemiological implications.

Methods and Results

As a novel tool for studying chlamydia, we applied principles of modeling within-host pathogen dynamics to enable an understanding of some fundamental characteristics of an individual''s immunobiology during multiple chlamydial infections. While the models were able to reproduce shorter-term infection kinetics of primary and secondary infections previously observed in animal models, it was also observed that longer periods between initial and second infection may increase an individual''s chlamydial load and lengthen their duration of infectiousness. The cessation of short-term repeated exposure did not allow for the formation of long-lasting immunity. However, frequent re-exposure non-intuitively linked the formation of protective immunity, persistent infection, and the potential for immunopathology.

Conclusions

Overall, these results provide interesting insights that should be verified with continued study. Nevertheless, these results appear to raise challenges for current evidence of the development of long-lasting immunity against chlamydia, and suggest the existence of a previously unidentified mechanism for the formation of persistent infection. The obvious next goal is to investigate the qualitative impact of these results on the spread of chlamydia.     

Transcriptional Profiling of Rats Subjected to Gestational Undernourishment: Implications for the Developmental Variations in Metabolic Traits

A link has been established between prenatal nutrition and the development of metabolic and cardiovascular diseases later in life, a process referred to as developmental programming. It has been suggested that the trajectory of development is shifted by alterations in the maternal nutritional state leading to changes in developmental plasticity, in part underpinned by epigenetic changes in gene regulation. However, to date, only candidate gene approaches have been used to assess expression and molecular changes in the offspring of maternally undernourished animals. Furthermore, most work has focused on animals at an age where the programmed phenotype is already manifest and little is known about changes in gene expression in the offspring prior to development of obesity and related metabolic disorders. Gene expression profiles of liver, retroperitoneal white adipose fat, and biceps femoris skeletal muscle tissue from young adult male rats (55 days old) in which nutritional status had been manipulated in utero by maternal undernutrition (UN) were compared to the profiles of offspring of ad libitum fed mothers serving as the control group (AD) (8 offspring/group). The expression profiles were determined using the Illumina RatRef-12 BeadChip. No significant changes in expression were identified for skeletal muscle or white adipose tissue. However, studies of liver tissue showed 249 differentially expressed genes (143 up regulated, 106 down regulated). Although the animals at day 55 have yet to develop obesity they already show biochemical abnormalities and by day 110 express a phenotype characterized by increased adiposity and altered insulin sensitivity. An analysis of pathways affected suggests that intrauterine programming of UN animals to favor fat as an energy source results in mitochondrial dysfunction which initially affects the postnatal hepatic function and subsequently, via the resultant metabolic changes in other organs leads to the evolution of a phenotype similar to that of the metabolic syndrome.     

Synthesis and structure-activity relationships of retro bis-aminopyrrolidine urea (rAPU) derived small-molecule antagonists of the melanin-concentrating hormone receptor-1 (MCH-R1). Part 2

The design, synthesis, and SAR of a series of retro bis-aminopyrrolidine ureas are described. Compounds from this series exhibited considerable binding affinity (Ki = 1 nM) and functional activity at MCH-R1, acceptable CYP2D6 inhibition, and good rat brain exposure.     

Deletion of cscR in Escherichia coli W improves growth and poly-3-hydroxybutyrate (PHB) production from sucrose in fed batch culture

Sucrose has several advantages over glucose as a feedstock for bioprocesses, both environmentally and economically. However, most industrial Escherichia coli strains are unable to utilize sucrose. E. coli W can grow on sucrose but stops growing when sucrose concentrations become low. This is undesirable in fed-batch conditions where sugar levels are low between feeding pulses. Sucrose uptake rates were improved by removal of the cscR gene, which encodes a protein that represses expression of the sucrose utilization genes at low sucrose concentrations. Poly-3-hydroxybutyrate (PHB) was used as a model compound in order to assess the effect of improved sugar utilization on bio-production. In the cscR knockout strain, production from sucrose was improved by 50%; this strain also produced 30% more PHB than the wild-type using glucose. This result demonstrates the feasibility of utilizing sucrose as an industrial feedstock for E. coli-based bioprocesses in high cell density culture.     

The application of a model of glucose and insulin dynamics to explain an observed effect of leptin administration in reversal of developmental programming

A dynamical model describing the glucose-insulin physiological system was applied to an experiment on the administration of the adipokine leptin between neonatal days 3 and 13 to rats whose dams were subject to different levels of nutrition during gestation. The effect of leptin treatment on the glucose-insulin equilibrium point and on the levels of other associated metabolites showed a significant change in direction that depended on the level of prenatal nutrition. Leptin has been shown to affect two factors that affect the equilibrium levels of glucose and insulin, gluconeogenesis and insulin sensitivity. Each effect is described by a parameter in the dynamical model. Mathematical analysis shows that changes in these parameters in the manner promoted by leptin would indeed increase or decrease the glucose-insulin equilibria depending on their initial equilibrium levels which might be induced by the level of prenatal nutrition. This analysis explains the results of the leptin experiment in the context of the dynamics of the glucocorticoid system. It also proposes a physiological mechanism for the expression of plasticity in the organism based on the status of the glucose and insulin equilibria.