Zinc: the Other Suspected Environmental Factor in Kashin-Beck Disease in Addition to Selenium

Kashin-Beck disease (KBD) is an endemic chronic osteochondral disease characterized by high prevalence, disability, and morbidity and is distributed from the northeast to the southwest in China, in some regions of Eastern Siberia in Russia, and in North Korea. Although the selenium deficiency etiological hypothesis for KBD has been proposed by scientists for decades, the idea that selenium deficiency is one of the most important environmental factors but not the primary and sole pathogenic factor for KBD has been widely accepted. Zn²⁺, which is closely involved in the synthesis of enzymes, nucleic acids, and proteins, is an essential microelement in vivo. A conundrum still exists in research on the relationship between Zn²⁺ and KBD due to inconsistent results, but it has been confirmed that Zn²⁺ can help repair metaphyseal lesions in patients with KBD, indicating that Zn²⁺ might play a key role in the pathogenesis of KBD, although the mechanism is unknown. The zinc-ZIP8-MTF1 axis in chondrocytes forms a catabolic cascade that promotes upregulation of the crucial effector matrix-degrading enzymes MMP3, MMP13, and ADAMTS5, thereby leading to osteoarthritis (OA) cartilage destruction. Zinc finger protein-related genes, the ZNT family, and the ZIP family of Zn²⁺ transporter genes have been found to be differentially expressed in KBD by high-throughput screening. Therefore, Zn²⁺ could play a key role in the pathogenesis of KBD.     

Ecology of Increasing Diseases: Population Growth and Environmental Degradation

The World Health Organization (WHO) and other organizations report that the prevalence of human diseases during the past decade is rapidly increasing. Population growth and the pollution of water, air, and soil are contributing to the increasing number of human diseases worldwide. Currently an estimated 40% of world deaths are due to environmental degradation. The ecology of increasing diseases has complex factors of environmental degradation, population growth, and the current malnutrition of about 3.7 billion people in the world.     

Feature Integration and Task Switching: Diminished Switch Costs after Controlling for Stimulus,Response, and Cue Repetitions

This report presents data from two versions of the task switching procedure in which the separate influence of stimulus repetitions, response key repetitions, conceptual response repetitions, cue repetitions, task repetitions, and congruency are considered. Experiment 1 used a simple alternating runs procedure with parity judgments of digits and consonant/vowel decisions of letters as the two tasks. Results revealed sizable effects of stimulus and response repetitions, and controlling for these effects reduced the switch cost. Experiment 2 was a cued version of the task switch paradigm with parity and magnitude judgments of digits as the two tasks. Results again revealed large effects of stimulus and response repetitions, in addition to cue repetition effects. Controlling for these effects again reduced the switch cost. Congruency did not interact with our novel “unbiased” measure of switch costs. We discuss how the task switch paradigm might be thought of as a more complex version of the feature integration paradigm and propose an episodic learning account of the effect. We further consider to what extent appeals to higher-order control processes might be unnecessary and propose that controls for feature integration biases should be standard practice in task switching experiments.     

From Defects to Degradation: A Mechanistic Understanding of Degradation in Perovskite Solar Cell Devices and Modules

Metal halide perovskite solar cells (PSCs) have risen in efficiency from just 3.81% in 2009 to over 25.2% today. While metal halide perovskites have excelled in efficiency, advances in stability are significantly more complex and have progressed more slowly. The advance of efficiency, which is readily measured, over stability, which can require literally thousands of hours to demonstrate, is to be expected given the rapid rate of innovation in the field. In the face of changing absorber composition, synthetic approaches, and device stack components it is necessary to understand basic material properties to rationalize how to enable stability in devices. In this article the aim is to present an in‐depth review of the current understanding of metal halide perovskite devices and module stability by focusing on what is known retarding intrinsic and extrinsic degradation mechanisms at the material, device, and module level. Once these considerations are presented the discussion then moves to connecting different degradation mechanisms to stresses anticipated in operation and how they can impact efficiency of cells and ultimately modules over time.     

Growth Hormone Changes in Chrysanthemum morifolium: Effects of Environmental Factors Controlling Flowering

Simultaneous quantitative analyses have been made of the endogenouslevels of auxin- and gibberellin like substances, growth inhibitors,and auxin-oxidizing enzyme activity in the cold-requiring Chrysanthemummorifolium cv. Sunbeam subjected to different daylength, lightintensity and temperature regimes known to affect flowering.While little hormone or enzyme activity was found in extractsfrom unvernalized plants, a striking rise in auxin-oxidizingenzyme activity occurred rapidly after the end of cold treatment.Increased auxin activity was also recorded shortly after vernalization.At 28 °C both enzyme and auxin activity declined over aperiod of 3–4 weeks; at 20 °C this response was delayed.Gibberellin activity at 28 °C rose steeply about 2 weeksfrom vernalization and declined several weeks later; at 20 °Ca similar response was less marked. Low light intensity treatment,which may have increased endogenous auxin levels, or exogenousauxin application reduced gibberellin-like substance levelsand cause d devernalization.Phosphon D treatment also loweredgibberellin levels and prevented flowering. An extract fromvernalized plants containing gibberellin-like substances intensifiedthe flowering of partially vernalized test plants. Persistenceof high auxin activity in vernalized plants on long days wasassociated with failure to form normal flower buds. Stem elongationrates correlated in general with levels of endogenous auxin-and gibberellin-like substances. Significant amounts of an abscisin-likeinhibitor were found in extracts of flower buds. The mechanismof natural devernalization is discussed in relation to theseobservations.     

The Hidden Health Burden of Environmental Degradation: Disease Comorbidities and Dryland Salinity

Previous studies have linked poor mental human health with environmental degradation, but none have assessed additional diseases that may co-exist with these mental disorders. In previous work, depression was found to be associated with a major form of environmental degradation; dryland salinity. However, little is known about diseases co-morbid with depression in this environmental setting. In rural Australia, dryland salinity is a major form of environmental degradation contributing widely to deterioration and non-viability of farmland. Using georeferenced health record data, Bayesian spatial methods were used to determine the relationship between dryland salinity and a range of human health outcomes. Initial modelling found an increased relative risk for asthma, suicide and ischaemic heart disease in relation to dryland salinity (adjusted for Indigenous and socio-economic status). However, in this follow-up study, a further evaluation of the role of co-morbidities in this population revealed that: (i) the presence of depression was consistently linked to residence in areas with high salinity and (ii) the association of asthma, suicide and heart disease with salinity was most likely attributable to the co-morbidity of the conditions with depression. Given the predicted increase in dryland salinity and the elevated relative risk of depression in impacted areas, the relative risk of the co-morbid conditions can be expected to increase in rural areas in the future, further adding to the burden of disease associated with environmental degradation.     

A Cellular Automaton Model for Tumor Dormancy: Emergence of a Proliferative Switch

Malignant cancers that lead to fatal outcomes for patients may remain dormant for very long periods of time. Although individual mechanisms such as cellular dormancy, angiogenic dormancy and immunosurveillance have been proposed, a comprehensive understanding of cancer dormancy and the “switch” from a dormant to a proliferative state still needs to be strengthened from both a basic and clinical point of view. Computational modeling enables one to explore a variety of scenarios for possible but realistic microscopic dormancy mechanisms and their predicted outcomes. The aim of this paper is to devise such a predictive computational model of dormancy with an emergent “switch” behavior. Specifically, we generalize a previous cellular automaton (CA) model for proliferative growth of solid tumor that now incorporates a variety of cell-level tumor-host interactions and different mechanisms for tumor dormancy, for example the effects of the immune system. Our new CA rules induce a natural “competition” between the tumor and tumor suppression factors in the microenvironment. This competition either results in a “stalemate” for a period of time in which the tumor either eventually wins (spontaneously emerges) or is eradicated; or it leads to a situation in which the tumor is eradicated before such a “stalemate” could ever develop. We also predict that if the number of actively dividing cells within the proliferative rim of the tumor reaches a critical, yet low level, the dormant tumor has a high probability to resume rapid growth. Our findings may shed light on the fundamental understanding of cancer dormancy.     

Response of Alpine Plants to Nitrogen Addition on the Tibetan Plateau: A Meta-analysis

To identify the general effects of nitrogen addition on alpine plants, we used a meta-analysis approach to synthesize 599 observations from 51 studies on the Tibetan Plateau. Nitrogen addition significantly increased plant height by 19.0 %, plant biomass by 29.7 %, graminoid aboveground biomass by 89.8 %, and sedge aboveground biomass by 75.6 % but significantly decreased legume aboveground biomass by 34.5 %, forb aboveground biomass by 23.8 %, and species richness by 11.2 %. The effect of nitrogen addition on aboveground plant biomass and plant height increased with increasing the nitrogen addition rate. The effect of nitrogen addition on plant height increased with increasing mean annual precipitation but decreased with increasing mean annual temperature. Our findings suggested that the effect of nitrogen addition on alpine plants varied with plant functional types and nitrogen addition rate. In addition, climatic warming and precipitation changes may regulate the response of alpine plants to nitrogen addition on the Tibetan Plateau.     

Neonatal Screening for Cystic Fibrosis: Addition of Molecular Diagnostics to Increase Specificity

Newborn screening for cystic fibrosis (CF) has been carried out on approximately 106,000 neonates in western Pennsylvania since 1987 using the immunoreactive trypsinogen (IRT) assay on dried filter paper blood specimens (DBS). Molecular analysis utilizing a duplicate DBS from the same sample was implemented in November 1989 for newborns having elevated IRT levels. DNA is amplified directly from the DBS and the amplified products are tested for the delta F508 deletion and several common exon 11 mutations. Substituting dUTP for dTTP in the PCR reaction and an initial treatment with uracil N-glycosylase (UNG) virtually eliminates PCR carryover contamination. The number of confirmed cases of CF is 20, giving an estimated incidence of 1:5287 in the western Pennsylvania population. Eight of the CF patients are homozygous and 12 are compound heterozygotes for the delta F508 deletion and a second mutation. Two of the compound heterozygotes carry the G551D mutation and one has the R553X mutation. Twenty-one additional neonates that are heterozygous for the delta F508 mutation are normal carriers for CF. In approximately 55% of the cases, molecular analysis of the CF gene confirmed the diagnosis of CF prior to sweat testing. The incorporation of molecular analysis into our CF screening program increases the specificity of the screening strategy and has the potential to decrease the false positive and sweat test referral rate, reduce parental anxiety, and bring CF infants to the attention of physicians more rapidly.     

承受生态恶果——塔河溯源行

正在消失的村落斯马伊·卡斯穆今年58岁,对于他来说,那些河水丰美的日子已经一去不返．对于他的后辈来说,则更像是一个传说了。我们相遇时,一场沙尘暴正在逐渐散去。     

Controlling Epithelial Polarity: A Human Enteroid Model for Host-Pathogen Interactions

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Risk and Decision-Making: A Workshop for Environmental Professionals

In the early 1990s, U.S. Environmental Protection Agency Region 9 developed a training workshop for environmental professionals. It was successfully taught throughout Region 9 in collaboration with the California Department of Toxic Substances Control. We have updated the workshop's manual to incorporate current practices including: vapor intrusion into indoor air, benchmark dose, cancer guidelines, inhalation guidance, ecological and screening risk assessments, conceptual site models, and data quality objectives. We maintained the popular workshop format, with participants evaluating information and drawing conclusions in an interactive hands-on approach. We kept the case study approach to simulate realistic environmental issues. After a case study introduction, participants plan a sampling strategy. Principles of toxicology are introduced, and participants develop toxicity criteria using hypothetical animal study results. Participants then identify exposure pathways, and calculate exposure and risk and hazard estimates. Finally, participants develop remedial alternatives and practice risk communication through role playing exercises. The workshop has been an effective tool for training new employees and providing continuing education for experienced employees from consulting, military, and regulatory agencies. The format provides a dynamic learning environment, fostering exchanges among professionals with a wide range of skills and backgrounds (project managers, toxicologists, geologists, engineers, public participation experts).     

A Method for Assessing Environmental Risks of Oil-Mineral-Aggregate to Benthic Organisms

Previous studies have shown that Oil-Mineral-Aggregate (OMA) formation enhances the dispersion of marine oil spills, but the potential impacts of settled OMAs on benthic organisms are not well known. A comprehensive numerical approach is proposed here to model the transport of OMAs and assesses their potential risks. The predicted environmental concentrations (PEC) of settled oil in OMAs was calculated using a random walk particle tracking model and the benchmark concentrations (BCs) of individual hydrocarbon groups were computed based on a equilibrium partitioning (EqP) approach. The likely of risks in terms of Hazard Quotient (HQ) were then determined using a Monte Carlo simulation method. HQ for both aliphatic and aromatic hydrocarbon groups were calculated for OMAs formed with two sediments, Mississippi River Delta (MRD) and Standard Reference Material (SRM). Mean total HQs were also determined by a simple sum of individual HQ. The predicted results from a case study based on a spill of 1000 tons of South Louisiana crude oil in the Gulf of St. Lawrence with a water depth of 80 m show that the SRM is unlikely to cause adverse impacts but this may not be the case for MRD. Furthermore, it has been found that the application of chemical dispersant (CD) increased the risks of MRD but it had little effects on SRM.     

Cell Blebbing upon Addition of Cryoprotectants: A Self-Protection Mechanism

In this work, the mechanism of cell bleb formation upon the addition of cryoprotectants (CPAs) was investigated, and the role of cell blebs in protecting cells was determined. The results show that after adding CPAs, the hyperosmotic stress results in the breakage of the cortical cytoskeleton and the detachment of the cell membrane from the cortical cytoskeleton, causing the formation of cell blebs. Multiple blebs decrease the intracellular hydrostatic pressure induced by the extracellular hyperosmotic shock and alleviate the osmotic damage to cells, which reduces the cell mortality rate. In the presence of a low concentration of CPAs, cell blebs can effectively protect cells. In contrast, in the presence of a high concentration of CPAs, the protective effect is limited because of severe disruption in the cortical cytoskeleton. To determine the relationship between blebs and the mortality rate of cells, we defined a bleb index and found that the bleb index of 0.065 can be regarded as a reference value for the safe addition of DMSO to HeLa cells. The bleb index can also explain why the stepwise addition of CPAs is better than the single-step addition of CPAs. Moreover, the mechanism of the autophagy of cells induced by the hyperosmotic stress was studied, and the protective effect associated with the autophagy was compared with the effect of the blebbing. The findings reported here elucidate a self-protection mechanism of cells experiencing the hyperosmotic stress in the presence of CPAs, and they provide significant evidence for cell tolerance in the field of cryopreservation.     

Anaerobic-Aerobic Process for Microbial Degradation of Tetrabromobisphenol A

Tetrabromobisphenol A (TBBPA) is a flame retardant that is used as an additive during manufacturing of plastic polymers and electronic circuit boards. Little is known about the fate of this compound in the environment. In the current study we investigated biodegradation of TBBPA, as well as 2,4,6-tribromophenol (TBP), in slurry of anaerobic sediment from a wet ephemeral desert stream bed contaminated with chemical industry waste. Anaerobic incubation of the sediment with TBBPA and peptone-tryptone-glucose-yeast extract medium resulted in a 80% decrease in the TBBPA concentration and accumulation of a single metabolite. This metabolite was identified by gas chromatography-mass spectrometry (GC-MS) as nonbrominated bisphenol A (BPA). On the other hand, TBP was reductively dehalogenated to phenol, which was further metabolized under anaerobic conditions. BPA persisted in the anaerobic slurry but was degraded aerobically. A gram-negative bacterium (strain WH1) was isolated from the contaminated soil, and under aerobic conditions this organism could use BPA as a sole carbon and energy source. During degradation of BPA two metabolites were detected in the culture medium, and these metabolites were identified by GC-MS and high-performance liquid chromatography as 4-hydroxybenzoic acid and 4-hydroxyacetophenone. Both of those compounds were utilized by WH1 as carbon and energy sources. Our findings demonstrate that it may be possible to use a sequential anaerobic-aerobic process to completely degrade TBBPA in contaminated soils.     

Catabolism of Pyrimidines in Yeast: A Tool to Understand Degradation of Anticancer Drugs

The pyrimidine catabolic pathway is of crucial importance in cancer patients because it is involved in degradation of several chemotherapeutic drugs, such as 5-fluorouracil; it also is important in plants, unicellular eukaryotes, and bacteria for the degradation of pyrimidine-based biocides/antibiotics. During the last decade we have developed a yeast species, Saccharomyces kluyveri, as a model and tool to study the genes and enzymes of the pyrimidine catabolic pathway. In this report, we studied degradation of uracil and its putative degradation products in 38 yeasts and showed that this pathway was present in the ancient yeasts but was lost approximately 100 million years ago in the S. cerevisiae lineage.     

The Addition of Dexfenfluramine to Fluoxetine in the Treatment of Obesity: A Randomized Clinical Trial

Current evidence demonstrates that pharmacologic agents, alone or in combination produce short-term weight-loss and may remain effective for extended periods of time in obese patients. We have evaluated the weight loss of a selective inhibitor of serotonin uptake, fluoxetine, alone as compared with combined therapeutic trial with another serotoninergic drug, dexfenfluramine. Thirty-three patients were randomly assigned in a double-blind randomized clinical trial divided to two groups: Group I [Fluoxetine 40 mg and placebo (n=13)] and Group II [Fluoxetine 40 mg plus dexfenfluramine 15 mg at night (n=20)]. Both groups had a significant weight loss at the end of 8 months (Group I, mean ± SEM 6.2 ± 2.8 kg and Group II 13.4 ± 6.3 kg, p < 0.05). Group II patients had a significantly greater weight loss as compared with Group I both in terms of mean weight loss in kg and BMI in kg/m². However significance between Group I and II related to BMI mean values and weight mean values were only achieved after, respectively, 4 and 6 months of treatment. At laboratory level there was an elevation of HDL-cholesterol and lowering of serum lipids values (cholesterol and triglycerides) in both groups. Side effects were relatively minor and no altered clinical vital signs or abnormal laboratory values were observed. We concluded that the combination of fluoxetine (daytime) and dexfenfluramine (at night) may be more effective than fluoxetine alone in weight reduction although the small size of this study does not permit broad generalization.