High salinity in drinking water creating pathways towards chronic poverty: A case study of coastal communities in Tanzania.

Seawater intrusion is a growing pressure in coastal communities worldwide, putting millions of people at risk of excess salinity in drinking water. This study examines the impact of saline water on people's health and labor allocation as potential pathways towards chronic poverty. Using a transdisciplinary approach based on a coupled human-water system framework, we test these linkages combining field data on well water salinity levels and rich household survey data in coastal Tanzania. The results suggest that increased salinity levels lead to more time spent collecting drinking water and an increase in illnesses. Moreover, households in poorer villages with weaker public infrastructure have limited access to alternative sources of drinking water, making them more vulnerable to scarce potable water resources stemming from high salinity. To prevent chronic poverty, communities vulnerable to saline drinking water need better adaptation strategies as well as groundwater monitoring and management.

TOPK is regulated by PP2A and BCR/ABL in leukemia and enhances cell proliferation.

Although treatment of chronic myeloid leukemia (CML) has improved with the development of tyrosine kinase inhibitors (TKIs), patients develop fatal blast crisis (BC) whilst receiving TKI treatment. Alternative treatments for cases resistant to TKIs are required. A serine/threonine protein kinase, T­lymphokine­activated killer cell­originated protein kinase (TOPK), is highly expressed in various malignant tumors. Binding of peptides to human leukocyte antigen was assessed via mass spectrometry in K562 CML cells. TOPK expression was assessed in various CML cell lines and in clinical samples obtained from patients with CML using reverse transcription­quantitative polymerase chain reaction and western blot assays. It was observed that TOPK was expressed abundantly in BCR/ABL­positive cell lines and at significantly higher levels in CML clinical samples compared with healthy donor samples. Overexpression of BCR/ABL or the presence of its inhibitor imatinib upregulated and downregulated TOPK expression, respectively, indicating that TOPK may be a target of BCR/ABL. TOPK inhibitor OTS514 suppressed proliferation of BCR/ABL­positive cell lines and colony formation of CD34­positive cells from patients with CML compared with lymphoma patients without bone marrow involvement. Furthermore, phosphorylation of TOPK was increased by protein phosphatase 2A (PP2A) inhibitor okadaic acid and was decreased in the presence of PP2A activator FTY720 compared with untreated samples. As constitutive BCR/ABL activity and inhibition of PP2A are key mechanisms of CML development, TOPK may be a crucial signaling molecule for this disease. Inhibition of TOPK may control disease status of CML, even in cases resistant to TKIs.

A multiscale approach to balance trade-offs among dam infrastructure, river restoration, and cost.

Aging infrastructure and growing interests in river restoration have led to a substantial rise in dam removals in the United States. However, the decision to remove a dam involves many complex trade-offs. The benefits of dam removal for hazard reduction and ecological restoration are potentially offset by the loss of hydroelectricity production, water supply, and other important services. We use a multiobjective approach to examine a wide array of trade-offs and synergies involved with strategic dam removal at three spatial scales in New England. We find that increasing the scale of decision-making improves the efficiency of trade-offs among ecosystem services, river safety, and economic costs resulting from dam removal, but this may lead to heterogeneous and less equitable local-scale outcomes. Our model may help facilitate multilateral funding, policy, and stakeholder agreements by analyzing the trade-offs of coordinated dam decisions, including net benefit alternatives to dam removal, at scales that satisfy these agreements.

Integrating watershed hydrology and economics to establish a local market for water quality improvement: A field experiment.

Innovative market mechanisms are being increasingly recognized as effective decision-making institutions to incorporate the value of ecosystem services into the economy. We present a field experiment that integrates an economic auction and a biophysical water flux model to develop a local market process consisting of both the supply and demand sides. On the supply side, we operate an auction with small-scale livestock owners who bid for contracts to implement site-specific manure management practices that reduce phosphorus loadings to a major reservoir. On the demand side, we implement a real money, multi-unit public good auction for these contracts with residents who potentially benefit from reduced water quality risks. The experiments allow us to construct supply and demand curves to find an equilibrium price for water quality improvement. The field experiments provide a proof-of-concept for practical implementation of a local market for environmental improvements, even for the challenging context of nonpoint pollution.

Aggressive TAFRO syndrome with reversible cardiomyopathy successfully treated with combination chemotherapy.

TAFRO (thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly) syndrome is an atypical manifestation of Castleman's disease. However, the mechanism underlying this very rare syndrome remains unknown, and there is no established standard treatment. Here we report cases of two young females with TAFRO syndrome who showed similar clinical courses. Both cases showed severe anasarca, ascites, and thrombocytopenia. Although high-dose steroids were ineffective, combination chemotherapy showed remarkable effects. However, both patients developed severe but reversible heart failure after CHOP therapy owing to diffuse cardiomyopathy, which was presumably associated with TAFRO syndrome. Therefore, although combination chemotherapy may be very effective in the treatment of TAFRO syndrome, careful observation for cardiomyopathy development is needed, particularly when using adriamycin-containing regimens.

[Refractory primary myeloid sarcoma of the breast with MLL-AF9 rearrangement].

A 28-year-old woman presented with a right breast mass and axillary lymphadenopathy. Biopsy of the breast mass revealed myeloid sarcoma (MS) staining positive for CD4, CD13, CD33, and CD68/KP-1. Bone marrow aspiration revealed leukemic cell infiltration (9%). Leukemic cells possessed cytogenetic abnormalities of +8 and t(9;11)(p22;q23) with +22 (lymph node only), and molecular analyses confirmed the MLL-AF9 fusion gene. After induction chemotherapy and 2(nd) consolidation therapy, complete remission was maintained. However, during consolidation radiotherapy for the breast mass, the disease progressed in both the breast and bone marrow. She received re-induction therapy and proceeded to allogeneic stem cell transplantation. However, the disease relapsed in the breast soon after transplantation, and she died from disease progression. Trisomy 8 and the MLL-AF9 fusion gene have been reported in cases with MS in the breast. Trisomy 22 found additionally and exclusively in the extramedullary lesion implies extramedullary progression of MS from the medullary site of origin and may have been associated with the distinctive therapy resistance of these lesions in our case.

Autoimmune Hemorrhaphilia Resulting from Autoantibody against the A Subunit of Factor XIII.

A 65-year-old woman was admitted with acute intramuscular hemorrhage of the left gluteus medius and piriformis muscles and associated anemia. Blood tests showed low plasma factor XIII (FXIII) antigen and activity. A cross-mixing test revealed a concave "inhibitor" pattern and anti-FXIII-A subunit antibody was detected. The patient was diagnosed with autoimmune hemorrhaphilia resulting from anti-FXIII antibody. The bleeding has not recurred since the initiation of treatment with oral immunosuppressive agents. Although hemorrhagic acquired FXIII deficiency is a rare disorder, prompt recognition of the underlying mechanism can save lives.

Light-induced crawling of crystals on a glass surface.

Motion is an essential process for many living organisms and for artificial robots and machines. To date, creating self-propelled motion in nano-to-macroscopic-sized objects has been a challenging issue for scientists. Herein, we report the directional and continuous motion of crystals on a glass surface when irradiated simultaneously with two different wavelengths, using simple azobenzenes as a photoresponsive organic compound. The direction of the motion can be controlled by the position of the light sources, and the crystals can even climb vertical surfaces. The motion is driven by crystallization and melting at the front and rear edges of the crystal, respectively, via photochemical conversion between the crystal and liquid phases induced by the trans-cis isomerization of azobenzenes. This finding could lead to remote-controlled micrometre-sized vehicles and valves on solid substrates.

Photoinduced crystal-to-liquid phase transitions of azobenzene derivatives and their application in photolithography processes through a solid-liquid patterning.

The direct and reversible transformation of matter between the solid and liquid phases by light at constant temperature is of great interest because of its potential applications in various manufacturing settings. We report a simple molecular design strategy for the phase transitions: azobenzenes having para-dialkoxy groups with a methyl group at the meta-position. The photolithography processes were demonstrated using the azobenzene as a photoresist in a single process combining development and etching of a copper substrate.

Macroscopic photocontrol of ion-transporting pathways of a nanostructured imidazolium-based photoresponsive liquid crystal.

The photocontrol of the macroscopic alignment of nanostructured 2D ion-transporting pathways is described. The uniplanar homogeneous alignment of the thermotropic smectic (Sm) liquid-crystalline (LC) phase has been successfully achieved via photoinduced reorientation of the azobenzene groups of the imidazolium-based LC material. The ionic layers of the Sm LC phase are macroscopically oriented perpendicular to the surface of the glass substrate. The oriented films show anisotropic ion conduction in the Sm phase. This is the first example of the macroscopic photoalignment of ion-conductive LC arrays. Reversible switching of homeotropic and homogeneous alignments has also been achieved for the LC material. These materials and the alignment methodology may be useful in the development of ion-based circuits and memory devices.

Crystal melting by light: X-ray crystal structure analysis of an azo crystal showing photoinduced crystal-melt transition.

Trans-cis photoisomerization in an azo compound containing azobenzene chromophores and long alkyl chains leads to a photoinduced crystal-melt transition (PCMT). X-ray structure analysis of this crystal clarifies the characteristic coexistence of the structurally ordered chromophores through their π···π interactions and disordered alkyl chains around room temperature. These structural features reveal that the PCMT starts near the surface of the crystal and propagates into the depth, sacrificing the π···π interactions. A temporal change of the powder X-ray diffraction pattern under light irradiation and a two-component phase diagram allow qualitative analysis of the PCMT and the following reconstructive crystallization of the cis isomer as a function of product accumulation. This is the first structural characterization of a compound showing the PCMT, overcoming the low periodicity that makes X-ray crystal structure analysis difficult.

Control of the orientation and photoinduced phase transitions of macrocyclic azobenzene.

Photoinduced phase transitions caused by photochromic reactions bring about a change in the state of matter at constant temperature. Herein, we report the photoinduced phase transitions of crystals of a photoresponsive macrocyclic compound bearing two azobenzene groups (1) at room temperature on irradiation with UV (365 nm) and visible (436 nm) light. The trans/trans isomer undergoes photoinduced phase transitions (crystal-isotropic phase-crystal) on UV light irradiation. The photochemically generated crystal exhibited reversible phase transitions between the crystal and the mesophase on UV and visible light irradiation. The molecular order of the randomly oriented crystals could be increased by irradiating with linearly polarized visible light, and the value of the order parameter was determined to be -0.84. Heating enhances the thermal cis-to-trans isomerization and subsequent cooling returned crystals of the trans/trans isomer.

A novel interplay between the Fanconi anemia core complex and ATR-ATRIP kinase during DNA cross-link repair.

When DNA replication is stalled at sites of DNA damage, a cascade of responses is activated in the cell to halt cell cycle progression and promote DNA repair. A pathway initiated by the kinase Ataxia teleangiectasia and Rad3 related (ATR) and its partner ATR interacting protein (ATRIP) plays an important role in this response. The Fanconi anemia (FA) pathway is also activated following genomic stress, and defects in this pathway cause a cancer-prone hematologic disorder in humans. Little is known about how these two pathways are coordinated. We report here that following cellular exposure to DNA cross-linking damage, the FA core complex enhances binding and localization of ATRIP within damaged chromatin. In cells lacking the core complex, ATR-mediated phosphorylation of two functional response targets, ATRIP and FANCI, is defective. We also provide evidence that the canonical ATR activation pathway involving RAD17 and TOPBP1 is largely dispensable for the FA pathway activation. Indeed DT40 mutant cells lacking both RAD17 and FANCD2 were synergistically more sensitive to cisplatin compared with either single mutant. Collectively, these data reveal new aspects of the interplay between regulation of ATR-ATRIP kinase and activation of the FA pathway.

Establishment of the DNA repair-defective mutants in DT40 cells.

The chicken B cell line DT40 has been widely used as a model system for reverse genetics studies in higher eukaryotes, because of its advantages including efficient gene targeting and ease of chromosome manipulation. Although the genetic approach using the RNA interference technique has become the standard method particularly in human cells, DT40 still remains a powerful tool to investigate the regulation and function of genes and proteins in a vertebrate system, because of feasibility of easy, rapid, and clear genetic experiments. The use of DT40 cells for DNA repair research has several advantages. In addition to canonical assays for DNA repair, such as measurement of the sensitivities toward DNA damage reagents, it is possible to measure homologous recombination and translesion synthesis activities using activation-induced deaminase (AID)-induced diversification of the immunoglobulin locus. In this chapter, we would describe a detailed protocol for gene disruption experiments in DT40 cells.

[Sequential monitoring of plasma EBV-DNA level in a patient with EBV-positive Hodgkin lymphoma].

A 58-year-old woman was admitted to our hospital because of fever, systemic lymphadenopathy with abnormal Epstein-Barr virus (EBV) antibody titers, and a high EBV-DNA load in the serum. She had been diagnosed as possibly having chronic active EBV infection (CAEBV) during a previous hospitalization. The EBV-DNA load of the plasma (pEBV-DNA), examined at our hospital, was elevated to 1.8×10(4) copies/ml, whereas that of the peripheral blood mononuclear cells was 3.4×10(1) copies/µg DNA, which was not clearly elevated, unlike in cases with CAEBV. Biopsy of the cervical lymph node was performed and the diagnosis of mixed cellularity classical Hodgkin lymphoma, Stage4B was made. Hodgkin cells were positive for EBV. COPP therapy was started and pEBV-DNA decreased drastically. The treatment was followed by ABVD therapy and pEBV-DNA turned negative after one course of ABVD therapy. She achieved complete response after 4 courses of the treatment. Reports from abroad indicate that pEBV-DNA parallels the disease state of EBV-positive Hodgkin lymphoma. Our results were consistent with these reports, and demonstrated that, in a Japanese patient, EBV-DNA load and its localization in the peripheral blood fractions could be useful tools for diagnosis as well as evaluating the disease status.

ATR-ATRIP kinase complex triggers activation of the Fanconi anemia DNA repair pathway.

ATR kinase activates the S-phase checkpoint when replication forks stall at sites of DNA damage. This event also causes phosphorylation of the Fanconi anemia (FA) protein FANCI, triggering its monoubiquitination of the key DNA repair factor FANCD2 by the FA core E3 ligase complex, thereby promoting this central pathway of DNA repair which permits replication to be restarted. However, the interplay between ATR and the FA pathway has been unclear. In this study, we present evidence that their action is directly linked, gaining insights into this relationship in a DT40 mutant cell line that is conditionally deficient in the critical ATR-binding partner protein ATRIP. Using this system, we showed that ATRIP was crucial for DNA damage-induced FANCD2 monoubiquitination and FANCI phosphorylation. ATR kinase phosphorylated recombinant FANCI protein in vitro, which was facilitated by the presence of FANCD2. Mechanistic investigations revealed that the RPA region but not the TopBP1 region of ATRIP was required for FANCD2 monoubiquitination, whereas Chk1 phosphorylation relied upon both domains. Together, our findings identify ATR as the kinase responsible for activating the FA pathway of DNA repair.

The effect of a protected area on the tradeoffs between short-run and long-run benefits from mangrove ecosystems.

Protected areas are used to sustain biodiversity and ecosystem services. However, protected areas can create tradeoffs spatially and temporally among ecosystem services, which can affect the welfare of dependent local communities. This study examines the effect of a protected area on the tradeoff between two extractive ecosystem services from mangrove forests: cutting mangroves (fuelwood) and harvesting the shrimp and fish that thrive if mangroves are not cut. We demonstrate the effect in the context of Saadani National Park (SANAPA) in Tanzania, where enforcement of prohibition of mangrove harvesting was strengthened to preserve biodiversity. Remote sensing data of mangrove cover over time are integrated with georeferenced household survey data in an econometric framework to identify the causal effect of mangrove protection on income components directly linked to mangrove ecosystem services. Our findings suggest that many households experienced an immediate loss in the consumption of mangrove firewood, with the loss most prevalent in richer households. However, all wealth classes appear to benefit from long-term sustainability gains in shrimping and fishing that result from mangrove protection. On average, we find that a 10% increase in the mangrove cover within SANAPA boundaries in a 5-km(2) radius of the subvillage increases shrimping income by approximately twofold. The creation of SANAPA shifted the future trajectory of the area from one in which mangroves were experiencing uncontrolled cutting to one in which mangrove conservation is providing gains in income for the local villages as a result of the preservation of nursery habitat and biodiversity.

Cost-effectiveness of payments for ecosystem services with dual goals of environment and poverty alleviation.

The goal of this article is to understand strategies by which both the environmental and poverty alleviation objectives of PES programs can be achieved cost effectively. To meet this goal, we first create a conceptual framework to understand the implications of alternative targeting when policy makers have both environmental and poverty alleviation goals. We then use the Grain for Green program in China, the largest PES program in the developing world, as a case study. We also use a data set from a survey that we designed and implemented to evaluate the program. Using the data set we first evaluate what factors determined selection of program areas for the Grain for Green program. We then demonstrate the heterogeneity of parcels and households and examine the correlations across households and their parcels in terms of their potential environmental benefits, opportunity costs of participating, and the asset levels of households as an indicator of poverty. Finally, we compare five alternative targeting criteria and simulate their performance in terms of cost effectiveness in meeting both the environmental and poverty alleviation goals when given a fixed budget. Based on our simulations, we find that there is a substantial gain in the cost effectiveness of the program by targeting parcels based on the "gold standard," i.e., targeting parcels with low opportunity cost and high environmental benefit managed by poorer households.

FANCI phosphorylation functions as a molecular switch to turn on the Fanconi anemia pathway.

In response to DNA damage or replication fork stress, the Fanconi anemia pathway is activated, leading to monoubiquitination of FANCD2 and FANCI and their colocalization in foci. Here we show that, in the chicken DT40 cell system, multiple alanine-substitution mutations in six conserved and clustered Ser/Thr-Gln motifs of FANCI largely abrogate monoubiquitination and focus formation of both FANCI and FANCD2, resulting in loss of DNA repair function. Conversely, FANCI carrying phosphomimic mutations on the same six residues induces constitutive monoubiquitination and focus formation of FANCI and FANCD2, and protects against cell killing and chromosome breakage by DNA interstrand cross-linking agents. We propose that the multiple phosphorylation of FANCI serves as a molecular switch in activation of the Fanconi anemia pathway. Mutational analysis of putative phosphorylation sites in human FANCI indicates that this switch is evolutionarily conserved.

Polarization gratings in twisted-nematic liquid-crystal composites doped with azobenzene dye.

Highly efficient and functionalized polarization gratings have been recorded in azobenzene-containing mesogenic composites with twisted nematic cell configurations. The polarization gratings formed in azobenzene-containing mesogenic composites show a high diffraction efficiency of more than 45% and convert the polarization state of light at the same time. The polarization direction of the diffracted laser beams can be controlled by the twisted angle of the nematic cell. These characteristics of the polarization gratings are well explained by means of Jones calculus.