Flow distributed oscillation, flow velocity modulation and resonance

We examine the effects of a periodically varying flow velocity on the standing and travelling wave patterns formed by the flow-distributed oscillation (FDO) mechanism. In the kinematic (or diffusionless) limit, the phase fronts undergo a simple, spatiotemporally periodic longitudinal displacement. On the other hand, when the diffusion is significant, periodic modulation of the velocity can disrupt the wave pattern, giving rise in the downstream region to travelling waves whose frequency is a rational multiple of the velocity perturbation frequency. We observe frequency locking at ratios of 1:1, 2:1 and 3:1, depending on the amplitude and frequency of the velocity modulation. This phenomenon can be viewed as a novel, rather subtle type of resonant forcing.Comment: submitted to Phys. Rev.

Extracellular electrical fields direct wound healing and regeneration

Author Posting. © Marine Biological Laboratory, 2011. This article is posted here by permission of Marine Biological Laboratory for personal use, not for redistribution. The definitive version was published in Biological Bulletin 221 (2011): 79-92.Endogenous DC electric fields (EFs) are important, fundamental components of development, regeneration, and wound healing. The fields are the result of polarized ion transport and current flow through electrically conductive pathways. Nullification of endogenous EFs with pharmacological agents or applied EFs of opposite polarity disturbs the aforementioned processes, while enhancement increases the rate of wound closure and the extent of regeneration. EFs are applied to humans in the clinic, to provide an overwhelming signal for the enhancement of healing of chronic wounds. Although clinical trials, spanning a course of decades, have shown that applied EFs enhance healing of chronic wounds, the mechanisms by which cells sense and respond to these weak cues remains unknown. EFs are thought to influence many different processes in vivo. However, under more rigorously controlled conditions in vitro, applied EFs induce cellular polarity and direct migration and outgrowth. Here we review the generation of endogenous EFs, the results of their alteration, and the mechanisms by which cells may sense these weak fields. Understanding the mechanisms by which native and applied EFs direct development and repair will enable current and future therapeutic applications to be optimized.This work has been supported by The Eugene and Millicent Bell Fellowship Fund in Tissue Engineering (M.A.M.), the Hermann Foundation Research Development Fund Award (M.A.M.), the NIH:NCRR grant P41 RR001395 (PI Peter JS Smith) and the Regenerative Biology Center at the MBL GM092374 (PI Gary Borisy)

A zinc transporter gene required for development of the nervous system.

The essentiality of zinc for normal brain development is well established. It has been suggested that primary and secondary zinc deficiencies can contribute to the occurrence of numerous human birth defects, including many involving the central nervous system. In a recent study, we searched for zinc transporter genes that were critical for neurodevelopment. We confirmed that ZIP12 is a zinc transporter encoded by the gene slc39a12 that is highly expressed in the central nervous systems of human, mouse, and frog (Xenopus tropicalis).Using loss-of-function methods, we determined that ZIP12 is required for neuronal differentiation and neurite outgrowth and necessary for neurulation and embryonic viability. These results highlight an essential need for zinc regulation during embryogenesis and nervous system development. We suggest that slc39a12 is a candidate gene for inherited neurodevelopmental defects in humans

Spatial manipulation of cells and organelles using single electrode dielectrophoresis

Author Posting. © Author(s), 2012. This article is posted here by permission of Informa Healthcare USA, for personal use, not for redistribution. The definitive version was published in BioTechniques 52 (2012): 39-43, doi:10.2144/000113802.The selection, isolation, and accurate positioning of single cells in three dimensions are increasingly desirable in many areas of cell biology and tissue engineering. We describe the application of a simple and low cost dielectrophoretic device for picking out and relocating single target cells. The device consists of a single metal electrode and an AC signal generator. It does not require microfabrication technologies or sophisticated electronics. The dielectrophoretic manipulator also discriminates between live and dead cells and is capable of redistributing intracellular organelles.This research was funded by NIH-NCRR grant P41 RR001395 and supported by The Eugene and Millicent Bell Fellowship Fund in Tissue Engineering, the Hermann Foundation Research Development Fund Award, the Dennis and Alix Robinson Memorial, and the MBL Bell Center, grant GM092374.2012-07-0

Cisplatin resistant spheroids model clinically relevant survival mechanisms in ovarian tumors

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS 11 (2016): e0151089, doi: 10.1371/journal.pone.0151089 .The majority of ovarian tumors eventually recur in a drug resistant form. Using cisplatin sensitive and resistant cell lines assembled into 3D spheroids we profiled gene expression and identified candidate mechanisms and biological pathways associated with cisplatin resistance. OVCAR-8 human ovarian carcinoma cells were exposed to sub-lethal concentrations of cisplatin to create a matched cisplatin-resistant cell line, OVCAR-8R. Genome-wide gene expression profiling of sensitive and resistant ovarian cancer spheroids identified 3,331 significantly differentially expressed probesets coding for 3,139 distinct protein-coding genes (Fc >2, FDR < 0.05) (S2 Table). Despite significant expression changes in some transporters including MDR1, cisplatin resistance was not associated with differences in intracellular cisplatin concentration. Cisplatin resistant cells were significantly enriched for a mesenchymal gene expression signature. OVCAR-8R resistance derived gene sets were significantly more biased to patients with shorter survival. From the most differentially expressed genes, we derived a 17-gene expression signature that identifies ovarian cancer patients with shorter overall survival in three independent datasets. We propose that the use of cisplatin resistant cell lines in 3D spheroid models is a viable approach to gain insight into resistance mechanisms relevant to ovarian tumors in patients. Our data support the emerging concept that ovarian cancers can acquire drug resistance through an epithelial-to-mesenchymal transition.This work was funded by the NIH NCRR supplement grant P41 RR001395-27S1 (J.W.H.), NSF DBI-1005378 “REU Site: Biological Discovery in Woods Hole”, faculty startup funds from the Office of Research at Oklahoma State University (W.C.), and the Mary Kay Foundation (A.S.B.)

Limnogeologúa de Laguna Chungará y cambio climático durante el Holoceno superior en el altiplano chileno septentrional

[Resumen] El estudio sísmico de la Laguna Chungará (69° 30' O, 18° 15'S, 4520 m. s.n.m, Altiplano chileno septentrional) y el análisis sedimentológico de varios sondeos ha permitido reconstruir la evolución de la sedimentación lacustre en el lago durante el Holoceno Superior. Se han identificado dos asociaciones de facies: i) litoral, más somera, compuesta por facies de turbera y in plataforma lacustre, más profunda, compuesta por facies con abundantes fragmentos de Characeae. Estas facies alternan en tres ciclos sedimentarios provocados por fluctuaciones en el nivel del lago. Estas variaciones hidrológicas en la laguna han sido causadas por cambios en el balance hídrico que a su vez reflejan importantes fluctuaciones climáticas durante el Holoceno Superior.[Abstract] We reconstruct the Late Holocene sedimentary history of Laguna Chungará (69° 30' W, 18° 10'5, 4520 m.a.s.l., northern Chilean Altiplano) based on high resolution seismic profiling and sedimentologic analyses of cores. Two sedimentary facies associations have been defined and interpreted: n macrophytedominant littoral, composed of black muds with macrophyte remains and peaty muds, and in Characeae-dominant lacustrine self, composed of gray muds and sands with abundant Characeae remains. The two facies associations define three cycles caused by oscillations in the lake level from shallower (macrophyte) to deeper (Characeae) conditions. Changes in the hydrology of Laguna Chungará reflect variations in the effective moisture (precipitation - evaporation) in the Altiplano during the Late Holocene

The Lausanne Infant Crying Stress Paradigm: Validation of an Early Postpartum Stress Paradigm with Women at Low vs. High Risk of Childbirth-Related Posttraumatic Stress Disorder.

Stress reactivity is typically investigated in laboratory settings, which is inadequate for mothers in maternity settings. This study aimed at validating the Lausanne Infant Crying Stress Paradigm (LICSP) as a new psychosocial stress paradigm eliciting psychophysiological stress reactivity in early postpartum mothers (n = 52) and to compare stress reactivity in women at low (n = 28) vs. high risk (n = 24) of childbirth-related posttraumatic stress disorder (CB-PTSD). Stress reactivity was assessed at pre-, peri-, and post-stress levels through salivary cortisol, heart rate variability (high-frequency (HF) power, low-frequency (LF) power, and LF/HF ratio), and perceived stress via a visual analog scale. Significant time effects were observed for all stress reactivity outcomes in the total sample (all p &lt; 0.01). When adjusting for perceived life threat for the infant during childbirth, high-risk mothers reported higher perceived stress (p &lt; 0.001, d = 0.91) and had lower salivary cortisol release (p = 0.023, d = 0.53), lower LF/HF ratio (p &lt; 0.001, d = 0.93), and marginally higher HF power (p = 0.07, d = 0.53) than low-risk women. In conclusion, the LICSP induces subjective stress and autonomic nervous system (ANS) reactivity in maternity settings. High-risk mothers showed higher perceived stress and altered ANS and hypothalamic-pituitary-adrenal reactivity when adjusting for infant life threat. Ultimately, the LICSP could stimulate (CB-)PTSD research

Effects of Verapamil SR and Atenolol on 24-Hour Blood Pressure and Heart Rate in Hypertension Patients with Coronary Artery Disease...

Elevated night-time blood pressure (BP) and heart rate (HR), increased BP and HR variability, and altered diurnal variations of BP and HR (nighttime dipping and morning surge) in patients with systemic hypertension are each associated with increased adverse cardiovascular events. However, there are no reports on the effect of hypertension treatment on these important hemodynamic parameters in the growing population of hypertensive patients with atherosclerotic coronary artery disease (CAD). This was a pre-specified subgroup analysis of the INternational VErapamil SR-Trandolapril STudy (INVEST), which involved 22,576 clinically stable patients aged ≥50 years with hypertension and CAD randomized to either verapamil SR- or atenolol-based hypertension treatment strategies. The subgroup consisted of 117 patients undergoing 24-hour ambulatory monitoring at baseline and after 1 year of treatment. Hourly systolic and diastolic BP (SBP and DBP) decreased after 1 year for both verapamil SR- and atenolol-based treatment strategies compared with baseline (P<0.0001). Atenolol also decreased hourly HR (P<0.0001). Both treatment strategies decreased SBP variability (weighted standard deviation: P = 0.012 and 0.021, respectively). Compared with verapamil SR, atenolol also increased the prevalence of BP and HR night-time dipping among prior non-dippers (BP: OR = 3.37; 95% CI: 1.26 – 8.97; P = 0.015; HR: OR = 4.06; 95% CI: 1.35-12.17;P = 0.012) and blunted HR morning surge (+2.8 vs. +4.5 beats/min/hr; P = 0.019). Both verapamil SR- and especially atenolol-based strategies resulted in favorable changes in ambulatory monitoring parameters that have been previously associated with increased adverse cardiovascular events

Effects of Verapamil SR and Atenolol on 24-Hour Blood Pressure and Heart Rate in Hypertension Patients with Coronary Artery Disease...

Elevated night-time blood pressure (BP) and heart rate (HR), increased BP and HR variability, and altered diurnal variations of BP and HR (nighttime dipping and morning surge) in patients with systemic hypertension are each associated with increased adverse cardiovascular events. However, there are no reports on the effect of hypertension treatment on these important hemodynamic parameters in the growing population of hypertensive patients with atherosclerotic coronary artery disease (CAD). This was a pre-specified subgroup analysis of the INternational VErapamil SR-Trandolapril STudy (INVEST), which involved 22,576 clinically stable patients aged ≥50 years with hypertension and CAD randomized to either verapamil SR- or atenolol-based hypertension treatment strategies. The subgroup consisted of 117 patients undergoing 24-hour ambulatory monitoring at baseline and after 1 year of treatment. Hourly systolic and diastolic BP (SBP and DBP) decreased after 1 year for both verapamil SR- and atenolol-based treatment strategies compared with baseline (P<0.0001). Atenolol also decreased hourly HR (P<0.0001). Both treatment strategies decreased SBP variability (weighted standard deviation: P = 0.012 and 0.021, respectively). Compared with verapamil SR, atenolol also increased the prevalence of BP and HR night-time dipping among prior non-dippers (BP: OR = 3.37; 95% CI: 1.26 – 8.97; P = 0.015; HR: OR = 4.06; 95% CI: 1.35-12.17;P = 0.012) and blunted HR morning surge (+2.8 vs. +4.5 beats/min/hr; P = 0.019). Both verapamil SR- and especially atenolol-based strategies resulted in favorable changes in ambulatory monitoring parameters that have been previously associated with increased adverse cardiovascular events

Mapping interactions between the sustainable development goals: lessons learned and ways forward

Pursuing integrated research and decision-making to advance action on the sustainable development goals (SDGs) fundamentally depends on understanding interactions between the SDGs, both negative ones (“trade-offs”) and positive ones (“co-benefits”). This quest, triggered by the 2030 Agenda, has however pointed to a gap in current research and policy analysis regarding how to think systematically about interactions across the SDGs. This paper synthesizes experiences and insights from the application of a new conceptual framework for mapping and assessing SDG interactions using a defined typology and characterization approach. Drawing on results from a major international research study applied to the SDGs on health, energy and the ocean, it analyses how interactions depend on key factors such as geographical context, resource endowments, time horizon and governance. The paper discusses the future potential, barriers and opportunities for applying the approach in scientific research, in policy making and in bridging the two through a global SDG Interactions Knowledge Platform as a key mechanism for assembling, systematizing and aggregating knowledge on interactions