Synergistic controls of water column stability and groundwater phosphate on coastal algal blooms.

Algal blooms have been identified as one major threat to coastal safety and marine ecosystem functioning, but the dominant mechanism regulating the formation of algal blooms remains controversial, ranging from physical control (via water column stability), the chemical control (via coastal nutrients) to joint control. Here we leveraged the unique data collected in the Hong Kong water over the annual cycle and past three decades, including direct observations of algal blooms and coastal nutrients and process model output of water column stability, and evaluated the differential competing hypotheses in regulating algal blooms. Our results demonstrate that the joint mechanism rather than the single mechanism effectively predicts all algal blooms. Meanwhile, we observed that the adequate nutrients (phosphate, PO43-) significantly originate from coastal groundwater. The production and fluctuation of PO43- in beach aquifers are primarily governed by groundwater temperature, leading to a sustained and sufficient supply of PO43- in a low groundwater temperature environment. Furthermore, along with submarine groundwater discharge (SGD), the ongoing release of PO43- in groundwater enters coastal waters and serves as sufficient nourishment for promoting algal blooms in coastal areas. These results highlight the importance of both physical and chemical mechanisms, as well as SGD, in regulating coastal algal blooms. These findings have practical implications for the prevention of coastal algal blooms and provide insights into mariculture, water security, and the sustainability of coastal ecosystems.

Storm accelerated subsurface Escherichia coli growth and exports to coastal waters.

Storm significantly deteriorates coastal water fecal pollution now and beyond. Questions relating to storm exerting on coastal water safety are often intertwined with both surface water and subsurface processes. Stormwater runoff is a vital metric for coastal water fecal pollution under current cognition, while the controls of subsurface system remain unclear. Here, this study leveraged two time-series field data collected in a sandy beach during storm and non-storm periods to probe subsurface Escherichia coli (E. coli) growth and exports to coastal waters under storm events. Results demonstrated that storm events can not only stimulate subsurface E. coli growth, but also accelerate subsurface E. coli exports into the receiving water. Storm-intensified rainfall injected more oxygenous rainwater in the shallow groundwater, subsequently stimulating subsurface E. coli growth. Storm-strengthened wave energy was responsible for accelerating subsurface E. coli exports through enhanced wave-induced recirculated seawater. This study proposes a new insight for the stress of storm events on microbial pollution in coastal waters. The findings are constructive to the prevention of beach ecosystem pollution and can pave the way for coastal safety management to future extreme weather.

Effective coastal Escherichia coli monitoring by unmanned aerial vehicles (UAV) thermal infrared images.

Coastal Escherichia coli (E. coli) significantly influence ocean safety and public health, thus requiring an effective E. coli pollution monitoring. However conventional detection relying on manual field sampling is time-consuming. Here, this study established an E. coli estimation model based on thermal remote sensing of unmanned aerial vehicles (UAV). This model was developed against one-year comprehensive field work in a representative sandy beach and further validated against 50 beaches in Hong Kong to evaluate its applicability. The estimated E. coli concentrations were in a reliable agreement with direct measurements. For this model, this study deployed the radon-222 (222Rn) as a bridging tracer to couple UAV thermal images and coastal E. coli concentrations. Coastal 222Rn can be reflected on the UAV thermal images, and there was a good positive correlation between the 222Rn activity and coastal E. coli concentration via one-year field data. Hence, coupling the 222Rn activity estimated from UAV thermal images and the relationship between 222Rn and E. coli, this study can readily monitor coastal E. coli by UAV. These findings highlighted that UAV technology is an effective approach to measure the E. coli concentrations and can further pave the way for an efficient coastal E. coli monitoring and public health risk warning.

Delineating E. coli occurrence and transport in the sandy beach groundwater system by radon-222.

Fecal pollution poses a global threat to environmental safety and ecosystem, but the mechanism of microbial transport and occurrence in the beach groundwater system is still poorly explored. Here, we leveraged one-year field data of Escherichia coli (E. coli) and radon-222 (222Rn) and found that E. coli occurrence and transport in the sandy beach groundwater system can be delineated by 222Rn. The underlying mechanism behind this phenomenon is due to similar half-lives of 222Rn and E. coli in the sandy beach groundwater system. Thus, the unique relationship between 222Rn and E. coli can provide additional critical context to the microbial water quality assessments and ecosystem resilience. Also, the beach aquifer in this study is found to be a vital compartment for E. coli removal. The net E. coli removal/production capacity is identified to be highly impacted by submarine groundwater discharge. Finally, a conceptual model is constructed for a better understanding of the occurrences and characteristics of E. coli and 222Rn at multiple spatial scales. These findings are constructive to mitigate the hazardous influences of microbe on water quality, especially in recreational sandy beaches and mariculture zones.

Two-decade variations of fresh submarine groundwater discharge to Tolo Harbour and their ecological significance by coupled remote sensing and radon-222 model.

Although submarine groundwater discharge (SGD) comprises an insignificant proportion of the global hydrologic cycle, it contributes significantly to chemical fluxes into the coastal waters due to concentrated constituents in coastal groundwater. Large nutrient loadings derived from SGD can lead to a series of environmental and ecological problems such as algal blooms, resulting in water discoloration, severe dissolved oxygen depletion, and eventually beach closures and massive fish kills. Previous studies have demonstrated the relationship between algal blooms and SGD obtained from direct measurement with seepage meters or from geo-tracer (i.e., radon and radium) based models; these traditional methods are time-consuming, laborious and point monitoring, and can hardly achieve a high spatiotemporal resolution SGD estimation, which is vital in revealing the effects of SGD to algal blooms over a long period. Alternatively, remote sensing methods for high spatiotemporal resolution SGD localization and quantification are applicable and effective. The temperature difference or anomaly between groundwater and coastal water extracted from satellite thermal images can be used as the indicator to localize and detect SGD especially its fresh component (or fresh SGD). In this study, multi-year (2005, 2011 and 2018) radon samples in Tolo Harbour were used to train regression models between in-situ radon (Rn) activity and the temperature anomaly by Landsat satellite thermal images. The models were used to estimate two-decade variations of fresh SGD in Tolo Harbour. The synergistic analysis between the time series of fresh SGD derived from regression models and high spatiotemporal resolution ecological metrics (chlorophyll-a, algal cell counts, and E.coli) leads to the findings that the increase of the fresh SGD associated with high nutrient concentrations is witnessed 10-20 days before the observations of algal bloom events. This study makes the first attempt to demonstrate the strong relation between the SGD and algal blooms over a vicennial span, and also provides a cost effective and robust technique to estimate SGD on a bay scale.

Remote sensing of coastal algal blooms using unmanned aerial vehicles (UAVs).

The explosive growth of phytoplankton under favorable conditions in subtropical coastal waters can lead to water discolouration and massive fish kills. Traditional water quality monitoring relies on manual field sampling and laboratory analysis of chlorophyll-a (Chl-a) concentration, which is resources intensive and time consuming. The cloudy weather of Hong Kong also precludes using satellite images for algal blooms monitoring. This study for the first time demonstrates the use of an Unmanned Aerial Vehicle (UAVs) to quantitatively map surface water Chl-a distribution in coastal waters from a low altitude. An estimation model for Chl-a concentration from visible images taken by a digital camera on a UAV has been developed and validated against one-year field data. The cost-effective and robust technology is able to map the spatial and temporal variations of Chl-a concentration during an algal bloom. The proposed method offers a useful complement to traditional field monitoring for fisheries management.

Collagen microsphere based 3D culture system for human osteoarthritis chondrocytes (hOACs).

The current study aims to evaluate collagen microencapsulation as an in vitro 3D culture platform for human osteoarthritic chondrocytes (hOACs), and to exemplify its feasibility in screening potential disease modifying factors. We first isolated and expanded hOACs from osteoarthritis (OA) cartilage samples harvested from multiple patients during total knee replacement (TKR) surgery. These cells were microencapsulated into collagen microspheres for subsequent 3D cultures. The change in chondrocyte phenotypes and OA phenotype was evaluated over time, using 2D monolayer culture and traditional 3D pellet culture as controls. The hOACs in the 3D collagen microsphere model resumed their in vivo phenotypes when compared to 2D monolayer. When compared with the 3D pellet model, the 3D hOAC-collagen microsphere model better recapitulated the OA phenotypes. We further demonstrated the responsiveness of the microencapsulated hOACs towards a number of external factors altering the chondrogenic phenotype, corroborating with previous studies. The hOAC encapsulated collagen microspheres better maintained the hOAC phenotype than the traditional 2D monolayer and 3D pellet cultures. The feasibility to use this hOAC-collagen microsphere in vitro model as a screening platform for disease-modifying agents has been demonstrated, contributing to future development of OA therapeutics.

Adipocytokines and proinflammatory mediators from abdominal and epicardial adipose tissue in patients with coronary artery disease.

OBJECTIVE: Epicardial and abdominal adipose tissues have recently been demonstrated to play inflammatory roles in coronary atherosclerosis. We sought to compare tissue adipocytokine levels of these two anatomically distinct adipose stores in patients with and without coronary artery diseases (CAD). DESIGN: Samples of abdominal and epicardial fat tissues were harvested to detect the levels of adipocytokines and proinflammatory mediators. SUBJECTS: Forty-six patients with CAD who underwent coronary artery bypass surgery and 12 non-CAD control subjects who underwent other types of open-heart surgery. MEASUREMENTS: Tissue levels of adipocytokines (adiponectin, leptin and visfatin) and proinflammatory mediators (tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)) were determined by enzyme-linked immunosorbent assay. RESULTS: Tissue levels of TNF-alpha, IL-6, leptin and visfatin were significantly higher in CAD patients relative to control subjects. In addition, significantly higher tissue levels of these four cytokines from abdominal fat depots were found compared to those from epicardial fat in CAD patients. Conversely, in comparison with control subjects, tissue levels of adiponectin were significantly reduced in CAD patients with a significantly lower tissue levels of abdominal than epicardial fat depots demonstrated. CONCLUSION: Abdominal adiposity may play more significant role than epicardial fat in the pathogenesis of coronary atherosclerosis.

Transoral vertical ramus osteotomy fixed with Kirschner pins.

Transoral vertical ramus osteotomy (VRO) has been condemned because the condyle has the potential to sag, and because it needs lengthy maxillomandibular fixation. We have therefore introduced a simple method of fixation, and examined its effectiveness and complications. After the osteotomy, the proximal and distal segments are trimmed to adapt to each other. Four Kirschner (K) pins 0.9mm in diameter are inserted percutaneously from the proximal to the distal segment while the condyle is positioned in the glenoid fossa. This is followed by a brief period of maxillomandibular fixation. We have reviewed the records of 95 patients who had unilateral or bilateral vertical ramus osteotomy fixed with K pins, after which the mean (SD) period of fixation was 19 (11) days. Fixation failed in two patients because excursion of the jaw was either too heavy or too early. The fixations were redone. All other fixations remained stable, including the 20 dual-jaw procedures in which VRO preceded maxillary osteotomy. The mean (SD) maximal mouth opening at final follow-up was 44 (7) mm, and in only one patient was it less than 30mm. Numbness of the lip or chin developed in seven patients, five of whom had other anterior mandibular procedures. Four patients had discomfort on palpation of the site of the pins, and one required removal. The new method was effective, and resulted in few complications within its limitations.

KLF10 loss in the pancreas provokes activation of SDF-1 and induces distant metastases of pancreatic ductal adenocarcinoma in the KrasG12D p53flox/flox model.

Krüppel-like transcription factor 10 (KLF10), also named as TIEG1, plays essential roles in mediating transforming growth factor beta (TGFß) signaling and has been shown to function as a tumor suppressor in multiple cancer types. However, its roles in mediating cancer progression in vivo have yet to be fully characterized. Here, we have employed two well-characterized Pdx-1CreLSL-KrasG12D and Pdx-1CreLSL-KrasG12Dp53L/L pancreatic cancer models to ablate KLF10 expression and determine the impact of KLF10 deletion on tumor development and progression. We show that loss of KLF10 cooperates with KrasG12D leading to an invasive and widely metastatic phenotype of pancreatic ductal adenocarcinoma (PDAC). Mechanistically, loss of KLF10 in PDAC is shown to increase distant metastases and cancer stemness through activation of SDF-1/CXCR4 and AP-1 pathways. Furthermore, we demonstrate that targeting the SDF-1/CXCR4 pathway in the context of KLF10 deletion substantially suppresses PDAC progression suggesting that inhibition of this pathway represents a novel therapeutic strategy for PDAC treatment.

Microfluidic-based diagnostics for cervical cancer cells.

The use of biomarkers has facilitated the detection of specific tumor cells. However, the technology to apply these markers in a clinical setting has not kept pace with their increasing availability. In this project, we use an antibody-based microfluidics platform to recognize and capture cervical cancer cells. Because HPV-16 infection of cervical cells and up-regulation of alpha6-integrin cell surface receptors are correlated, we utilized alpha6-integrin as a capture antibody bound to the channel surface. Normal human glandular epithelial cells (HGEC), human cervical stromal cells (HCSC) and cervical cancer cells (HCCC) were suspended in PBS and flowed through the system. Greater than 30% of the cancer cells were captured while the capture of the normal cell types was less than 5%. The technique is sensitive and accurate. It is potentially useful in the detection of cervical cancer at all stages, as well as other of cancers with similar characteristics of cell surface antigen expression.

Role of calcium in the thermal inactivation of calcium transport proteins.

Using purified sarcoplasmic reticulum membranes as model systems, the role of calcium ion in the thermal inactivation of membrane calcium transport was investigated. Hyperthermia induces calcium release from the heavy fraction of sarcoplasmic reticulum. This calcium channel related calcium release was inhibited by the presence of glycerol and enhanced by the presence of ethanol. Calcium was found to protect the thermal-induced calcium transport inactivation of CaATPase in the light fraction of sarcoplasmic reticulum. Both glycerol and cholesterol protect the thermal inactivation of CaATPase. Yet their effects on the calcium-induced protection kinetics were rather different, i.e., the glycerol inserts its protection effect by increasing the degree of cooperativity of calcium binding, while cholesterol increases the calcium-binding affinity. The calcium protection effect was attributed to the ability of calcium to enhance the thermal stability of the protein. This was demonstrated by an upshift (30-39 degrees C) of the transition temperature of the rotational parameter of the native tryptophans of CaATPase in the presence of calcium.

Magnetic resonance diffusion imaging detects structural damage in biological tissues upon hyperthermia.

The use of quantitative nuclear magnetic resonance (MR) imaging to investigate the extent and mechanism of hyperthermic damage in biological tissues has been studied. By using the multiple delay-multiple echo and pulsed-gradient spin echo MR imaging sequences, multiple frame MR images of freshly harvested rabbit tissues (brain, kidney, and muscle) and intact duck embryos in shells were obtained before and after heat treatment (45 degrees C for 30 min) using a clinical 1.5-Tesla whole-body superconducting MR scanner. Based on the relaxation and diffusion models, maps of the proton spin density, relaxation times, and various self-diffusion parameters of tissue water were generated from these multiple frame MR images. Our results indicated that the values of the diffusion barrier size and fractal parameter of the tissues and the self-diffusion coefficient of tissue water increased significantly, i.e., approached that of free water, after the heat treatment. In comparison, only slight changes in the spin density and relaxation times of the tissue water were found after the identical heat treatment. We concluded that the significant changes in the self-diffusive behavior of the tissue water are due to the denaturation of macromolecules (e.g., protein and fiber) within the tissues at elevated temperatures. We further suggested that MR diffusion imaging represents a powerful tool to investigate the extent and mechanism of heat damage of biological tissues in vivo and therefore bears important potential in the clinical assessment of the therapeutic efficacy of hyperthermia in cancer therapy.

Protection of the membrane calcium adenosine triphosphatase by cholesterol from thermal inactivation.

There is correlative evidence that one mechanism of cellular thermoresistance is an increased level of membrane cholesterol. The hypothesis that cholesterol protects membrane proteins from thermal inactivation was tested using Ca-ATPase as a model. The intracellular Ca2+- and Mg2+-dependent ATPase from muscle sarcoplasmic reticulum was reconstituted into lipid mixtures containing different amounts of cholesterol [cholesterol/phospholipid molar ratio (C/PL) = 0.1 or 0.3]. The rate of thermal inactivation of calcium uptake activity of the reconstituted vesicles with C/PL = 0.3 was found to be significantly lower than those with C/PL = 0.1 in the temperature range 43-47 degrees C where hyperthermic cell killing occurs. At 43 degrees C, this is equivalent to a 3 degrees C temperature shift. ATP hydrolysis of Ca-ATPase was found to be substantially heat resistant in reconstituted vesicles with C/PL = 0.1 or 0.3. Glycerol (10%) protects while ethanol (2.5%) and the local anesthetics dibucaine, tetracaine, and procaine sensitize the thermal inactivation of calcium uptake. To investigate the molecular mechanisms of thermal inactivation and cholesterol protection, the responses of the physical state of the lipid and protein conformation to hyperthermic sensitizers and protector were monitored using fluorescent and spin label probes and circular dichroism, respectively. The calcium uptake inactivation appears to be due to a direct thermotropic conformational change (denaturation) of the protein. Cholesterol raises the temperature of inactivation, as does glycerol, while ethanol and the local anesthetics lower it.

APC haploinsufficiency coupled with p53 loss sufficiently induces mucinous cystic neoplasms and invasive pancreatic carcinoma in mice.

Adenomatous polyposis coli (APC), a tumor-suppressor gene critically involved in familial adenomatous polyposis, is integral in Wnt/ß-catenin signaling and is implicated in the development of sporadic tumors of the distal gastrointestinal tract including pancreatic cancer (PC). Here we report for the first time that functional APC is required for the growth and maintenance of pancreatic islets and maturation. Subsequently, a non-Kras mutation-induced premalignancy mouse model was developed; in this model, APC haploinsufficiency coupled with p53 deletion resulted in the development of a distinct type of pancreatic premalignant precursors, mucinous cystic neoplasms (MCNs), exhibiting pathomechanisms identical to those observed in human MCNs, including accumulation of cystic fluid secreted by neoplastic and ovarian-like stromal cells, with 100% penetrance and the presence of hepatic and gastric metastases in >30% of the mice. The major clinical implications of this study suggest targeting the Wnt signaling pathway as a novel strategy for managing MCN.

Lateral organisation of membrane lipids. The superlattice view.

Most biological membranes are extremely complex structures consisting of hundreds or even thousands of different lipid and protein molecules. The prevailing view regarding the organisation of these membranes is based on the fluid-mosaic model proposed by Singer and Nicholson in 1972. According to this model, phospholipids together with some other lipids form a fluid bilayer in which these lipids are diffusing very rapidly laterally. The idea of rapid lateral diffusion implies that, in general, the different lipid species would be randomly distributed in the plain of the membrane. However, there are recent data indicating that the components tend to adopt regular (superlattice-like) distributions in fluid, mixed bilayers. Based on this, a superlattice model of membranes has been proposed. This superlattice model is intriguing because it allows only a limited certain number of 'critical' compositions. These critical compositions could play a key role in the regulation of the lipid compositions of biological membranes. Furthermore, such putative critical compositions could explain how compositionally distinct organelles can exist despite of rapid inter-organelle membrane traffic. In this review, these intriguing predictions are discussed along with the basic principles of the model and the evidence supporting it.

Mass spectra and time-resolved fluorescence spectroscopy of the reaction product of glycine with 1,2-indanedione in methanol.

The reaction products of 1,2-indanedione (a new fluorescent fingerprint reagent) with glycine in methanol, at room temperature have been studied using excitation and emission and time-resolved fluorescence spectroscopy. Gas chromatography-mass spectroscopy (GC/MS) has also been used to determine which compounds are formed. Reaction products were identified using GC/MS as 2-carboxymethyliminoindanone (MW=203 g) and 1,2-di(carboxymethylimino)indane (MW=260 g). Identified compounds show room temperature fluorescence lifetimes of tau(1)=7.69 ns and tau(2)=1.27 ns. It is not clear yet which compound is having fluorescence lifetime of 7.69 ns and which one is showing 1.27 ns.

Microdosimetry spectra and relative biological effectiveness of 15 and 30MeV proton beams.

The relative biological effectiveness (RBE) of high-energy protons has been well investigated, but estimates of RBE for lower-energy (<40MeV) protons are scarce. In the present work, measurements were made of the lineal energy spectra using a home-made miniature tissue-equivalent proportional counter for 15 and 30MeV protons from the TR 30/15 cyclotron. Monte Carlo simulations were made for the same spectra using the FLUKA code. These spectra were coupled to several biological models to evaluate the RBE for various biological endpoints.

The interaction of serum testosterone levels and androgen receptor CAG repeat polymorphism on the risk of erectile dysfunction in aging Taiwanese men.

Testosterone has been found to play important roles in men's sexual function. However, the effects of testosterone can be modulated by androgen receptor (AR) CAG repeat polymorphism. It could also contribute to the risk of erectile dysfunction (ED). The aim of this study is to evaluate the interaction of serum testosterone levels and AR CAG repeat polymorphism on the risk of ED in aging Taiwanese men. This cross-sectional data of Taiwanese men older than 40 years were collected from a free health screening held between August 2010 and August 2011 in Kaohsiung city, Taiwan. All participants completed a health questionnaires included five-item version of the International Index of Erectile Function (IIEF-5) and the International Prostate Symptoms Score, received a detailed physical examination and provided 20 cm3 whole blood samples for biochemical and genetic evaluation. The IIEF-5 was used to evaluate ED. Serum albumin, total testosterone (TT), and sex hormone-binding globulin levels were measured. Free testosterone level was calculated. AR gene CAG repeat polymorphism was determined by direct sequencing. Finally, 478 men with the mean age of 55.7 ± 4.8 years were included. When TT levels were above 330 ng/dL, the effect of testosterone level on erectile function seemed to reach a plateau and a significantly negative correlation between AR CAG repeat length and the score of IIEF-5 was found (r = -0.119, p = 0.034). After adjusting for other covariates, the longer AR CAG repeat length was still an independent risk factor for ED in subjects with TT above 330 ng/dL (p = 0.006), but not in TT of 330 ng/dL or below. In conclusion, both serum testosterone levels and AR CAG repeat polymorphism can influence erectile function concomitantly. In subjects with normal TT concentration, those with longer AR CAG repeat lengths have a higher risk of developing ED.

Selective binding of a 30-kilodalton protein to disposable hydrophilic contact lenses.

To investigate the accumulation of tear proteins on disposable extended-wear contact lenses (42% Etafilcon A and 58% hydration), a technique involving sodium dodecyl sulfate-polyacrylamide minigel electrophoresis combined with a sensitive silver-staining method was used. Besides the binding of large amounts of tear lysozyme the authors found an accumulation of an as yet unidentified 30-kilodalton (kD) protein. Longitudinal experiments showed lysozyme binding after 1 day of lens wear. The 30-kD protein was detected after a 2-day wearing period. The fact that protein deposition occurs during the relatively short wearing period of these lenses (1 week) may explain the unexpectedly high incidence of contact lens-associated conjunctivitis observed with these lenses.