Sex differences in kidney gene expression during the life cycle of F344 rats

Background

The kidney functions in key physiological processes to filter blood and regulate blood pressure via key molecular transporters and ion channels. Sex-specific differences have been observed in renal disease incidence and progression, as well as acute kidney injury in response to certain drugs. Although advances have been made in characterizing the molecular components involved in various kidney functions, the molecular mechanisms responsible for sex differences are not well understood. We hypothesized that the basal expression levels of genes involved in various kidney functions throughout the life cycle will influence sex-specific susceptibilities to adverse renal events.

Methods

Whole genome microarray gene expression analysis was performed on kidney samples collected from untreated male and female Fischer 344 (F344) rats at eight age groups between 2 and 104 weeks of age.

Results

A combined filtering approach using statistical (ANOVA or pairwise t test, FDR 0.05) and fold-change criteria (>1.5 relative fold change) was used to identify 7,447 unique differentially expressed genes (DEGs). Principal component analysis (PCA) of the 7,447 DEGs revealed sex-related differences in mRNA expression at early (2 weeks), middle (8, 15, and 21 weeks), and late (104 weeks) ages in the rat life cycle. Functional analysis (Ingenuity Pathway Analysis) of these sex-different genes indicated over-representation of specific pathways and networks including renal tubule injury, drug metabolism, and immune cell and inflammatory responses. The mRNAs that code for the qualified urinary protein kidney biomarkers KIM-1, Clu, Tff3, and Lcn2 were also observed to show sex differences.

Conclusions

These data represent one of the most comprehensive in-life time course studies to be published, assessing sex differences in global gene expression in the F344 rat kidney. PCA and Venn analyses reveal specific periods of sexually dimorphic gene expression which are associated with functional categories (xenobiotic metabolism and immune cell and inflammatory responses) of key relevance to acute kidney injury and chronic kidney disease, which may underlie sex-specific susceptibility. Analysis of the basal gene expression patterns of renal genes throughout the life cycle of the rat will improve the use of current and future renal biomarkers and inform our assessments of kidney injury and disease.

     

Global marine bacterial diversity peaks at high latitudes in winter

Genomic approaches to characterizing bacterial communities are revealing significant differences in diversity and composition between environments. But bacterial distributions have not been mapped at a global scale. Although current community surveys are way too sparse to map global diversity patterns directly, there is now sufficient data to fit accurate models of how bacterial distributions vary across different environments and to make global scale maps from these models. We apply this approach to map the global distributions of bacteria in marine surface waters. Our spatially and temporally explicit predictions suggest that bacterial diversity peaks in temperate latitudes across the world''s oceans. These global peaks are seasonal, occurring 6 months apart in the two hemispheres, in the boreal and austral winters. This pattern is quite different from the tropical, seasonally consistent diversity patterns observed for most macroorganisms. However, like other marine organisms, surface water bacteria are particularly diverse in regions of high human environmental impacts on the oceans. Our maps provide the first picture of bacterial distributions at a global scale and suggest important differences between the diversity patterns of bacteria compared with other organisms.     

Age and menopause affect the expression of specific cytokines/chemokines in plasma and cervical lavage samples from female sex workers in Nairobi,Kenya

Background

Aging of the immune system, known as immunosenescence, is associated with profound changes in both innate and adaptive immune responses, resulting in increased susceptibility to infection and a decreased ability to respond to vaccination. The purpose of this study was to investigate the effect of age and menopause on the expression of 22 different cytokines/chemokines in both plasma and cervical lavage samples from female sex-worker cohort from Nairobi, Kenya (age range 20–65).

Results

Cytokine/chemokine levels were measured using a Miliplex multiplex assay (Millipore). We found that age positively correlated with MCP-1 (p?=?0.0002) and IP-10 (p?=?0.03) systemic cytokine expression, and that women over 50 expressed the highest levels of these cytokines, but also had elevated expression of MIG (ANOVA p?=?0.0096) and MIP-3β(ANOVA p?=?0.0434). We also found that IL-8 (p?=?0.047) and sCD40L (p?=?0.01) systemic expression negatively correlated with age. Further, MIG (p?=?0.0081) and MCP-1 (p?=?0.0157) were present at higher levels in post-menopausal women suggesting a potential estrogen dependant systemic regulation of these cytokines. In cervical lavage samples, age did not directly correlate with the expression of any of the tested cytokines/chemokines, however sIL-2Rα (ANOVA p?=?0.0170) and IL-15 (ANOVA p?=?0.0251)were significantly higher in women over 50. Menopause was shown to have a more profound effect on cytokine expression in the cervical mucosa with MIG (p?=?0.0256), MIP-3α (p?=?0.0245), IL-1β (p?=?0.0261), IL-6 (p?=?0.0462), IL-8 (p?=?0.007), IP-10 (p?=?0.0357) and MCP-1 (p?=?0.0427) all significantly under-expressed in post-menopausal women.

Conclusions

This study demonstrates that aging and menopause-associated hormonal changes are associated with significant changes in systemic and mucosal cytokine/chemokine expression, which may have implications for the age-related decline in the ability to fight against infections.

     

Metapopulation Dynamics Enable Persistence of Influenza A,Including A/H5N1, in Poultry

Highly pathogenic influenza A/H5N1 has persistently but sporadically caused human illness and death since 1997. Yet it is still unclear how this pathogen is able to persist globally. While wild birds seem to be a genetic reservoir for influenza A, they do not seem to be the main source of human illness. Here, we highlight the role that domestic poultry may play in maintaining A/H5N1 globally, using theoretical models of spatial population structure in poultry populations. We find that a metapopulation of moderately sized poultry flocks can sustain the pathogen in a finite poultry population for over two years. Our results suggest that it is possible that moderately intensive backyard farms could sustain the pathogen indefinitely in real systems. This fits a pattern that has been observed from many empirical systems. Rather than just employing standard culling procedures to control the disease, our model suggests ways that poultry production systems may be modified.     

The Congruency Effect in the Posterior Medial Frontal Cortex Is More Consistent with Time on Task than with Response Conflict

The posterior medial frontal cortex (pMFC) is thought to play a pivotal role in enabling the control of attention during periods of distraction. In line with this view, pMFC activity is ubiquitously greater in incongruent trials of response-interference (e.g., Stroop) tasks than in congruent trials. Nonetheless, the process underlying this congruency effect remains highly controversial. We therefore sought to distinguish between two competing accounts of the congruency effect. The conflict monitoring account posits the effect indexes a process that detects conflict between competing response alternatives, which is indexed by trial-specific reaction time (RT). The time on task account posits the effect indexes a process whose recruitment increases with time on task independent of response conflict (e.g., sustained attention, arousal, effort, etc.). To distinguish between these accounts, we used functional MRI to record brain activity in twenty-four healthy adults while they performed two tasks: a response-interference task and a simple RT task with only one possible response. We reasoned that demands on a process that detects response conflict should increase with RT in the response-interference task but not in the simple RT task. In contrast, demands on a process whose recruitment increases with time on task independent of response conflict should increase with RT in both tasks. Trial-by-trial analyses revealed that pMFC activity increased with RT in both tasks. Moreover, pMFC activity increased with RT in the simple RT task enough to fully account for the congruency effect in the response-interference task. These findings appear more consistent with the time on task account of the congruency effect than with the conflict monitoring account.     

Maternal and Perinatal Outcomes of Twin Pregnancy in 23 Low- and Middle-Income Countries

Background

Twin pregnancies in low- and middle-income countries (LMICs) pose a high risk to mothers and newborns due to inherent biological risks and scarcity of health resources. We conducted a secondary analysis of the WHO Global Survey dataset to analyze maternal and perinatal outcomes in twin pregnancies and factors associated with perinatal morbidity and mortality in twins.

Methods

We examined maternal and neonatal characteristics in twin deliveries in 23 LMICs and conducted multi-level logistic regression to determine the association between twins and adverse maternal and perinatal outcomes.

Results

279,425 mothers gave birth to 276,187 (98.8%) singletons and 6,476 (1.2%) twins. Odds of severe adverse maternal outcomes (death, blood transfusion, ICU admission or hysterectomy) (AOR 1.85, 95% CI 1.60–2.14) and perinatal mortality (AOR 2.46, 95% CI 1.40–4.35) in twin pregnancies were higher, however early neonatal death (AOR 2.50, 95% CI 0.95–6.62) and stillbirth (AOR 1.22, 95% CI 0.58–2.57) did not reach significance. Amongst twins alone, maternal age <18, poor education and antenatal care, nulliparity, vaginal bleeding, non-cephalic presentations, birth weight discordance >15%, born second, preterm birth and low birthweight were associated with perinatal mortality. Marriage and caesarean section were protective.

Conclusions

Twin pregnancy is a significant risk factor for maternal and perinatal morbidity and mortality in low-resource settings; maternal risk and access to safe caesarean section may determine safest mode of delivery in LMICs. Improving obstetric care in twin pregnancies, particularly timely access to safe caesarean section, is required to reduce risk to mother and baby.     

The Role of L-DOPA on Melanization and Mycelial Production in Malassezia Furfur

Melanins are synthesized by organisms of all biological kingdoms and comprise a heterogeneous class of natural pigments. Certain of these polymers have been implicated in the pathogenesis of several important human fungal pathogens. This study investigated whether the fungal skin pathogen Malassezia furfur produces melanin or melanin-like compounds. A melanin-binding monoclonal antibody (MAb) labelled in vitro cultivated yeast cells of M. furfur. In addition, melanization of Malassezia yeasts and hyphae was detected by anti-melanin MAb in scrapings from patients with pityriasis versicolor. Treatment of Malassezia yeasts with proteolytic enzymes, denaturant and concentrated hot acid yielded dark particles and electron spin resonance spectroscopy revealed that these particles contained a stable free radical compound, consistent with their identification as melanins. Malassezia yeasts required phenolic compounds, such as L-DOPA, in order to synthesize melanin. L-DOPA also triggered hyphal formation in vitro when combined with kojic acid, a tyrosinase inhibitor, in a dose-dependent manner. In this respect, L-DOPA is thought to be an essential substance that is linked to both melanization and yeast-mycelial transformation in M. furfur. In summary, M. furfur can produce melanin or melanin-like compounds in vitro and in vivo, and the DOPA melanin pathway is involved in cell wall melanization.     

New Tests to Measure Individual Differences in Matching and Labelling Facial Expressions of Emotion,and Their Association with Ability to Recognise Vocal Emotions and Facial Identity

Although good tests are available for diagnosing clinical impairments in face expression processing, there is a lack of strong tests for assessing “individual differences” – that is, differences in ability between individuals within the typical, nonclinical, range. Here, we develop two new tests, one for expression perception (an odd-man-out matching task in which participants select which one of three faces displays a different expression) and one additionally requiring explicit identification of the emotion (a labelling task in which participants select one of six verbal labels). We demonstrate validity (careful check of individual items, large inversion effects, independence from nonverbal IQ, convergent validity with a previous labelling task), reliability (Cronbach’s alphas of.77 and.76 respectively), and wide individual differences across the typical population. We then demonstrate the usefulness of the tests by addressing theoretical questions regarding the structure of face processing, specifically the extent to which the following processes are common or distinct: (a) perceptual matching and explicit labelling of expression (modest correlation between matching and labelling supported partial independence); (b) judgement of expressions from faces and voices (results argued labelling tasks tap into a multi-modal system, while matching tasks tap distinct perceptual processes); and (c) expression and identity processing (results argued for a common first step of perceptual processing for expression and identity).