Developmental Regulation of an Adhesin Gene during Cellular Morphogenesis in the Fungal Pathogen Candida albicans

Peer reviewedPublisher PD

A 6,000-year record of environmental change from the eastern Pacific margin of central Mexico

The transition from the mid- to late-Holocene in MesoAmerica saw increasing complexity in spatial patterns of change. Records from the western part of the region are sparse, with lacustrine sequences affected by long term anthropogenic disturbance or lacking chronological resolution. Here, we present a continuous palaeoecological and geochemical record from Laguna de Juanacatlán, a remote lake in the mountains of the western TMVB. Diatom assemblages, XRF scanning data and bulk organic geochemistry from a well-dated, 7.25-m laminated sequence were combined with summary pollen data from a 9-m partially laminated core to provide a continuous record of catchment and lake ecosystem changes over the last c. 6,000 years. Relatively humid conditions prevailed prior to c. 5.1 cal ka, which supported dense oak-pine forest cover around a deep, stratified lake. A trend towards drier conditions began c. 5.1 cal ka, intensifying after 4.0 cal ka, consistent with weakening of the North American Monsoon. Between 3.0 and 1.2 cal ka, lower lake levels and variable catchment run-off are consistent with increasing ENSO influence observed in the Late Holocene in the neotropics. From 1.2 to 0.9 cal ka, a marked change to catchment stability and more intense stratification reflected drier conditions and / or reduced rainfall variability and possibly warmer temperatures. After 0.9 cal ka, conditions were wetter, with an increase in catchment disturbance associated with the combined effects of climate and human activity. In recent decades, the lake ecosystem has changed markedly, possibly in response to recent climate change as well as local catchment dynamics

Reproductive Health Disparities: Pap Knowledge and Screening Rates among Asian Pacific Islander College Women

A Papanicolaou test is the most effective procedure for detecting cervical cancer. Unfortunately, many young Asian Pacific Islander (API) college women are unaware of this procedure and do not take precaution against cervical cancer. This paper reports disaggregated data on Pap knowledge and screening rates of female students at a four-year university and suggests recommendations to healthcare providers to improve Pap screening rates. Using a communitybased participatory research (CBPR) approach, a cross-sectional study was administered using a web-based anonymous survey (N=618). The survey results indicated that participants who were least likely to know about Pap tests were 18-21 years old, API, uninsured, and not in a committed relationship. Slightly more than half (52%) of API females received a screening compared to 82.4% of white females. The most influential people for Pap screening were doctors (43%) and the least influential people were mothers (18.8%) and friends (7.8%). This study expands the literature on Pap knowledge and screenings among API college students and provides culturally appropriate recommendations to improve screening rates

E2F1 and p53 Are Dispensable, whereas p21Waf1/Cip1 Cooperates with Rb to Restrict Endoreduplication and Apoptosis during Skeletal Myogenesis

AbstractWe describe temporal and genetic analyses of partially rescued Rb mutant fetuses, mgRb:Rb−/−, that survive to birth and reveal specific defects in skeletal muscle differentiation. We show that in the absence of Rb, these fetuses exhibit increased apoptosis, bona fide endoreduplication, and incomplete differentiation throughout terminal myogenesis. These defects were further augmented in composite mutant fetuses, mgRb:Rb−/−:p21−/−, lacking both Rb and the cyclin-dependent kinase inhibitor p21Waf1/Cip1. Although E2F1 and p53 mediate ectopic DNA synthesis and cell death in several tissues in Rb mutant embryos, both endoreduplication and apoptosis persisted in mgRb:Rb−/−:E2F1−/− and mgRb:Rb−/−:p53−/− compound mutant muscles. Thus, combined inactivation of Rb and p21Waf1/Cip1 augments endoreduplication and apoptosis, whereas E2F1 and p53 are dispensable during aberrant myogenesis in Rb-deficient fetuses

Plasma Levels of Macrophage Migration Inhibitory Factor and d-Dopachrome Tautomerase Show a Highly Specific Profile in Early Life.

Macrophage migration inhibitory factor (MIF) is a pleiotropic, constitutively expressed, pro-inflammatory cytokine and an important regulator of immune responses. d-dopachrome tautomerase (DDT), a newly described member of the MIF protein superfamily, shares sequence homology and biological activities with MIF. We recently reported that high expression levels of MIF sustain innate immune responses in newborns. Here, we elected to further characterize age-dependent MIF expression and to define whether DDT shares a similar expression profile with MIF. Therefore, we delineated the circulating concentrations of MIF and DDT throughout life using a large cohort of 307 subjects including fetuses, newborns, infants, children, and adults. Compared to levels measured in healthy adults (median: 5.7 ng/ml for MIF and 16.8 ng/ml for DDT), MIF and DDT plasma concentrations were higher in fetuses (median: 48.9 and 29.6 ng/ml), increased further at birth (median: 82.6 and 52.0 ng/ml), reached strikingly elevated levels on postnatal day 4 (median: 109.5 and 121.6 ng/ml), and decreased to adult levels during the first months of life. A strong correlation was observed between MIF and DDT concentrations in all age groups (R = 0.91, P < 0.0001). MIF and DDT levels correlated with concentrations of vascular endothelial growth factor, a protein upregulated under low oxygen tension and implicated in vascular and lung development (R = 0.70, P < 0.0001 for MIF and R = 0.65, P < 0.0001 for DDT). In very preterm infants, lower levels of MIF and DDT on postnatal day 6 were associated with an increased risk of developing bronchopulmonary dysplasia and late-onset neonatal sepsis. Thus, MIF and DDT plasma levels show a highly specific developmental profile in early life, supporting an important role for these cytokines during the neonatal period

Response of a low elevation carbonate lake in the Yucatan Peninsula (Mexico) to climatic and human forcings

The importance of climate change, specifically drought, across the Maya region in the northern Neotropics, remains a topic of lively debate. Part of this discussion hinges on the coherency of response to climatic variability across different archives and proxies. In this paper we present a 6600-year palaeolimnological record from Yaal Chac, a carbonate lake (known locally as a cenote) in the northern lowlands of the Yucatan Peninsula, 2‰), but show no covariation with δ13C. A major transition occurs at ca. 4360 cal yr BP, with a change to generally more organic sediments and increased variability in all proxies. Although direct evidence for anthropogenic activity in the Yaal Chac catchment is limited, it seems feasible that human impact was affecting the system. Comparison with other records from the Northern Maya lowlands and the wider region shows little coherence in the mid Holocene, when Yaal Chac seems to have been quite stable, but possibly responsive to increased climatic seasonality, driving the production of seasonal laminae. In the late Holocene, when the climate was generally more variable, there is more coherence between Yaal Chac and other regional records, including the so called Pan Caribbean Dry Period (3500–2500 cal yr BP) and the droughts of the late Pre-Classic period (1800–1600 cal yr BP). The Yaal Chac record shows no evidence of drought at the time of either the Maya ‘hiatus’ or the Maya ‘collapse’ of the Terminal Classic, but does record drying from the 14th to 19th centuries CE, in keeping with other proxy and historical records. This new record from Yaal Chac highlights the spatial variability of responses to climate forcings and the importance of recognising individual system sensitivity

RNA Sequencing Reveals Diverse Functions of Amniotic Fluid Neutrophils and Monocytes/Macrophages in Intra-Amniotic Infection

Intra-amniotic infection, the invasion of microbes into the amniotic cavity resulting in inflammation, is a clinical condition that can lead to adverse pregnancy outcomes for the mother and fetus as well as severe long-term neonatal morbidities. Despite much research focused on the consequences of intra-amniotic infection, there remains little knowledge about the innate immune cells that respond to invading microbes. We performed RNA-seq of sorted amniotic fluid neutrophils and monocytes/macrophages from women with intra-amniotic infection to determine the transcriptomic differences between these innate immune cells. Further, we sought to identify specific transcriptomic pathways that were significantly altered by the maternal or fetal origin of amniotic fluid neutrophils and monocytes/macrophages, the presence of a severe fetal inflammatory response, and pregnancy outcome (i.e., preterm or term delivery). We show that significant transcriptomic differences exist between amniotic fluid neutrophils and monocytes/macrophages from women with intra-amniotic infection, indicating the distinct roles these cells play. The transcriptome of amniotic fluid immune cells varies based on their maternal or fetal origin, and the significant transcriptomic differences between fetal and maternal monocytes/macrophages imply that those of fetal origin exhibit impaired functions. Notably, transcriptomic changes in amniotic fluid monocytes/macrophages suggest that these immune cells collaborate with neutrophils in the trafficking of fetal leukocytes throughout the umbilical cord (i.e., funisitis). Finally, amniotic fluid neutrophils and monocytes/macrophages from preterm deliveries display enhanced transcriptional activity compared to those from term deliveries, highlighting the protective role of these cells during this vulnerable period. Collectively, these findings demonstrate the underlying complexity of local innate immune responses in women with intra-amniotic infection and provide new insights into the functions of neutrophils and monocytes/macrophages in the amniotic cavity. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements

The determinants of food choice

Health nudge interventions to steer people into healthier lifestyles are increasingly applied by governments worldwide, and it is natural to look to such approaches to improve health by altering what people choose to eat. However, to produce policy recommendations that are likely to be effective, we need to be able to make valid predictions about the consequences of proposed interventions, and for this, we need a better understanding of the determinants of food choice. These determinants include dietary components (e.g. highly palatable foods and alcohol), but also diverse cultural and social pressures, cognitive-affective factors (perceived stress, health attitude, anxiety and depression), and familial, genetic and epigenetic influences on personality characteristics. In addition, our choices are influenced by an array of physiological mechanisms, including signals to the brain from the gastrointestinal tract and adipose tissue, which affect not only our hunger and satiety but also our motivation to eat particular nutrients, and the reward we experience from eating. Thus, to develop the evidence base necessary for effective policies, we need to build bridges across different levels of knowledge and understanding. This requires experimental models that can fill in the gaps in our understanding that are needed to inform policy, translational models that connect mechanistic understanding from laboratory studies to the real life human condition, and formal models that encapsulate scientific knowledge from diverse disciplines, and which embed understanding in a way that enables policy-relevant predictions to be made. Here we review recent developments in these areas.</p

A mouse model with a frameshift mutation in the nuclear factor I/X (NFIX) gene has phenotypic features of Marshall-Smith syndrome

The nuclear factor I/X (NFIX) gene encodes a ubiquitously expressed transcription factor whose mutations lead to two allelic disorders characterized by developmental, skeletal, and neural abnormalities, namely, Malan syndrome (MAL) and Marshall–Smith syndrome (MSS). NFIX mutations associated with MAL mainly cluster in exon 2 and are cleared by nonsense-mediated decay (NMD) leading to NFIX haploinsufficiency, whereas NFIX mutations associated with MSS are clustered in exons 6–10 and escape NMD and result in the production of dominant-negative mutant NFIX proteins. Thus, different NFIX mutations have distinct consequences on NFIX expression. To elucidate the in vivo effects of MSS-associated NFIX exon 7 mutations, we used CRISPR-Cas9 to generate mouse models with exon 7 deletions that comprised: a frameshift deletion of two nucleotides (Nfix Del2); in-frame deletion of 24 nucleotides (Nfix Del24); and deletion of 140 nucleotides (Nfix Del140). Nfix+/Del2, Nfix+/Del24, Nfix+/Del140, NfixDel24/Del24, and NfixDel140/Del140 mice were viable, normal, and fertile, with no skeletal abnormalities, but NfixDel2/Del2 mice had significantly reduced viability (p Nfix Del2 was not cleared by NMD, and NfixDel2/Del2 mice, when compared to Nfix+/+ and Nfix+/Del2 mice, had: growth retardation; short stature with kyphosis; reduced skull length; marked porosity of the vertebrae with decreased vertebral and femoral bone mineral content; and reduced caudal vertebrae height and femur length. Plasma biochemistry analysis revealed NfixDel2/Del2 mice to have increased total alkaline phosphatase activity but decreased C-terminal telopeptide and procollagen-type-1-N-terminal propeptide concentrations compared to Nfix+/+ and Nfix+/Del2 mice. NfixDel2/Del2 mice were also found to have enlarged cerebral cortices and ventricular areas but smaller dentate gyrus compared to Nfix+/+ mice. Thus, NfixDel2/Del2 mice provide a model for studying the in vivo effects of NFIX mutants that escape NMD and result in developmental abnormalities of the skeletal and neural tissues that are associated with MSS

Potential applications of wastes from energy generation particularly biochar in Malaysia.

In Malaysia, abundant agricultural wastes are generated yearly. Therefore it is beneficial to discover new ways to utilize the wastes and employ the carbon source in different industries. Biochar are produced through many heat treatments such as combustion, gasification and pyrolysis for energy generation. The characteristics of these stable carbons such as the physical properties, chemical composition, surface area and surface chemistry determine the effectiveness of the cabon in different applications. Biochar has the ability to retain carbon and this condition is advantageous to prevent the release of carbon back to the atmosphere in the form of carbon dioxide. Application of biochar to soil helps to improve soil fertility and raise agricultural productivity. Biochar also has the ability to reduce carbon dioxide in the flue gas system. There have only been a few studies that discuss on the potential applications of this agriculture waste. The biochar's potential application as carbon sequester for soil application, energy production and dye sorption is being explored in this paper