Mycoplasma genitalium among Young, Urban Pregnant Women

Objective. As the consequences of Mycoplasma genitalium in pregnant women are unknown, we examined the relationship between prenatal M. genitalium infection and SAB. Methods. The presence of M. genitalium was determined by PCR in urine from 82 women who subsequently experienced a SAB and 134 women who maintained their pregnancies past 22 weeks gestation. The relationships between M. genitalium and subsequent SAB, demographic, current pregnancy, and reproductive health history characteristics were evaluated. Results. Compared to women without M. genitalium, women with M. genitalium were more likely to report nulliparity (41.7% versus 17.4%, P = .04), history of pelvic inflammatory disease (27.3% versus 8.8%, P = .08), prior C. trachomatis infection (63.6% versus 36.9%, P = .11,) and problems getting pregnant (18.2% versus 4.4%, P = .10). M. genitalium was not associated with SAB (AOR 0.9, 95% CI 0.2–3.8). Conclusions. Pregnant women who test positive for M. genitalium do not have an increased risk of SAB but report a history of reproductive morbidities

Mutations in DYNC2LI1 disrupt cilia function and cause short rib polydactyly syndrome.

The short rib polydactyly syndromes (SRPSs) are a heterogeneous group of autosomal recessive, perinatal lethal skeletal disorders characterized primarily by short, horizontal ribs, short limbs and polydactyly. Mutations in several genes affecting intraflagellar transport (IFT) cause SRPS but they do not account for all cases. Here we identify an additional SRPS gene and further unravel the functional basis for IFT. We perform whole-exome sequencing and identify mutations in a new disease-producing gene, cytoplasmic dynein-2 light intermediate chain 1, DYNC2LI1, segregating with disease in three families. Using primary fibroblasts, we show that DYNC2LI1 is essential for dynein-2 complex stability and that mutations in DYNC2LI1 result in variable length, including hyperelongated, cilia, Hedgehog pathway impairment and ciliary IFT accumulations. The findings in this study expand our understanding of SRPS locus heterogeneity and demonstrate the importance of DYNC2LI1 in dynein-2 complex stability, cilium function, Hedgehog regulation and skeletogenesis

An Expanded Biological Repertoire for Ins(3,4,5,6)P4 through its Modulation of ClC-3 Function

Ins(3,4,5,6)P4 inhibits plasma membrane Cl− flux in secretory epithelia [1]. However, in most other mammalian cells, receptor-dependent elevation of Ins(3,4,5,6)P4 levels is an “orphan” response that lacks biological significance [2]. We set out to identify Cl− channel(s) and/or transporter(s) that are regulated by Ins(3,4,5,6)P4 in vivo. Several candidates [3-5] were excluded through biophysical criteria, electrophysiological analysis, and confocal immunofluorescence microscopy. Then, we heterologously expressed ClC-3 in the plasma membrane of HEK293-tsA201 cells; whole-cell patch-clamp analysis showed Ins(3,4,5,6)P4 to inhibit Cl− conductance through ClC-3. Next, we heterologously expressed ClC-3 in the early endosomal compartment of BHK cells; by fluorescence ratio imaging of endocytosed FITC-transferrin, we recorded intra-endosomal pH, an in situ biosensor for Cl− flux across endosomal membranes [6]. A cell-permeant, bioactivatable Ins(3,4,5,6)P4 analog elevated endosomal pH from 6.1 to 6.6, reflecting inhibition of ClC-3. Finally, Ins(3,4,5,6)P4 inhibited endogenous ClC-3 conductance in postsynaptic membranes of neonatal hippocampal neurones. Among other ClC-3 functions that could be regulated by Ins(3,4,5,6)P4 are tumor cell migration [7], apoptosis [8], and inflammatory responses [9]. Ins(3,4,5,6)P4 is a ubiquitous cellular signal with diverse biological actions

Prediction of the export and fate of global ocean net primary production : the EXPORTS Science Plan

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Frontiers in Marine Science 3 (2016): 22, doi:10.3389/fmars.2016.00022.Ocean ecosystems play a critical role in the Earth's carbon cycle and the quantification of their impacts for both present conditions and for predictions into the future remains one of the greatest challenges in oceanography. The goal of the EXport Processes in the Ocean from Remote Sensing (EXPORTS) Science Plan is to develop a predictive understanding of the export and fate of global ocean net primary production (NPP) and its implications for present and future climates. The achievement of this goal requires a quantification of the mechanisms that control the export of carbon from the euphotic zone as well as its fate in the underlying “twilight zone” where some fraction of exported carbon will be sequestered in the ocean's interior on time scales of months to millennia. Here we present a measurement/synthesis/modeling framework aimed at quantifying the fates of upper ocean NPP and its impacts on the global carbon cycle based upon the EXPORTS Science Plan. The proposed approach will diagnose relationships among the ecological, biogeochemical, and physical oceanographic processes that control carbon cycling across a range of ecosystem and carbon cycling states leading to advances in satellite diagnostic and numerical prognostic models. To collect these data, a combination of ship and robotic field sampling, satellite remote sensing, and numerical modeling is proposed which enables the sampling of the many pathways of NPP export and fates. This coordinated, process-oriented approach has the potential to foster new insights on ocean carbon cycling that maximizes its societal relevance through the achievement of research goals of many international research agencies and will be a key step toward our understanding of the Earth as an integrated system.The development of the EXPORTS Science Plan was supported by NASA Ocean Biology and Biogeochemistry program (award NNX13AC35G)

The patchwork governance of ecologically available water: A case study in the Upper Missouri Headwaters, Montana, United States

Institutional authority and responsibility for allocating water to ecosystems (“ecologically available water” [EAW]) is spread across local, state, and federal agencies, which operate under a range of statutes, mandates, and planning processes. We use a case study of the Upper Missouri Headwaters Basin in southwestern Montana, United States, to illustrate this fragmented institutional landscape. Our goals are to (a) describe the patchwork of agencies and institutional actors whose intersecting authorities and actions influence the EAW in the study basin; (b) describe the range of governance mechanisms these agencies use, including laws, policies, administrative programs, and planning processes; and (c) assess the extent to which the collective governance regime creates gaps in responsibility. We find the water governance regime includes a range of nested mechanisms that in various ways facilitate or hinder the governance of EAW. We conclude the current multilevel governance regime leaves certain aspects of EAW unaddressed and does not adequately account for the interconnections between water in different parts of the ecosystem, creating integrative gaps. We suggest that more intentional and robust coordination could provide a means to address these gaps

Digital Extended Specimens: Enabling an Extensible Network of Biodiversity Data Records as Integrated Digital Objects on the Internet

The early twenty-first century has witnessed massive expansions in availability and accessibility of digital data in virtually all domains of the biodiversity sciences. Led by an array of asynchronous digitization activities spanning ecological, environmental, climatological, and biological collections data, these initiatives have resulted in a plethora of mostly disconnected and siloed data, leaving to researchers the tedious and time-consuming manual task of finding and connecting them in usable ways, integrating them into coherent data sets, and making them interoperable. The focus to date has been on elevating analog and physical records to digital replicas in local databases prior to elevating them to ever-growing aggregations of essentially disconnected discipline-specific information. In the present article, we propose a new interconnected network of digital objects on the Internet—the Digital Extended Specimen (DES) network—that transcends existing aggregator technology, augments the DES with third-party data through machine algorithms, and provides a platform for more efficient research and robust interdisciplinary discovery

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine