Reservoir bathymetry and riparian corridor assessment in two dammed sections of the Teesta River in Eastern Himalaya.

As of mid-2021, four hydroelectric dams are operational on the main channel of the Teesta River in the mountainous and tectonically active Sikkim-Darjeeling-Kalimpong region of India. Riparian ecological and fluvial morphological changes after damming have not been documented. This paper describes an early study of a section of the middle Teesta River, at two of the dam-created reservoirs, just before the river enters the plains. High-resolution, multi-beam, geo-located sonar was used to map the bathymetry of the reservoirs. This resulted in the creation of 30cm-resolution bathymetric maps of the two reservoirs showing valley bottom morphology within them. The bathymetric maps were compared with pre-dam digital elevation models of the valley to create topographic change-maps. The change-maps indicate significant differences in valley morphology due to erosion and deposition processes. Land cover changes due to inundation were quantified from analysis of satellite imagery time series data of the reservoir riparian zones. Land cover change analysis showed a loss of ~ 74,000 trees in ~ 225 ha of flooded riparian corridors due to long-term inundation. The study shows that the dams have caused 7.4% of the river length to become quasi-lentic, and drastically altered sediment dynamics and hydrologic flow. Sediment deposition calculations indicate the reservoirs losing almost three-quarters of their surface areas to sediment deposition features within 15 years. This study will serve as an important baseline for future studies, and influence design and policy regarding riparian and fluvial ecosystem management, monitoring, and evaluation in the Teesta and similar mountainous river basins in the Eastern Himalaya.

BET-ting on Nrf2: How Nrf2 Signaling can Influence the Therapeutic Activities of BET Protein Inhibitors.

BET proteins such as Brd3 and Brd4 are chromatin-associated factors, which control gene expression programs that promote inflammation and cancer. The Nrf2 transcription factor is a master regulator of genes that protect the organism against xenobiotic attack and oxidative stress. Nrf2 has demonstrated anti-inflammatory activity and can support cancer cell malignancy. This review describes the discovery, mechanism and biomedical implications of the regulatory interplay between Nrf2 and BET proteins. Both Nrf2 and BET proteins are established drug targets. Small molecules that either activate or suppress these proteins are currently tested in clinical trials. The crosstalk between Nrf2 and BET proteins may have important, and until now overlooked, implications for the therapeutic effects of these drugs. Based on the information covered in this review, it should be possible to design combinatorial treatment strategies for cancer and inflammatory diseases, which may improve the efficacy of targeting a Nrf2 or BET proteins individually.

Keap1-Independent Regulation of Nrf2 Activity by Protein Acetylation and a BET Bromodomain Protein.

Mammalian BET proteins comprise a family of bromodomain-containing epigenetic regulators with complex functions in chromatin organization and gene regulation. We identified the sole member of the BET protein family in Drosophila, Fs(1)h, as an inhibitor of the stress responsive transcription factor CncC, the fly ortholog of Nrf2. Fs(1)h physically interacts with CncC in a manner that requires the function of its bromodomains and the acetylation of CncC. Treatment of cultured Drosophila cells or adult flies with fs(1)h RNAi or with the BET protein inhibitor JQ1 de-represses CncC transcriptional activity and engages protective gene expression programs. The mechanism by which Fs(1)h inhibits CncC function is distinct from the canonical mechanism that stimulates Nrf2 function by abrogating Keap1-dependent proteasomal degradation. Consistent with the independent modes of CncC regulation by Keap1 and Fs(1)h, combinations of drugs that can specifically target these pathways cause a strong synergistic and specific activation of protective CncC- dependent gene expression and boosts oxidative stress resistance. This synergism might be exploitable for the design of combinatorial therapies to target diseases associated with oxidative stress or inflammation.

Identification of specific DNA binding residues in the TCP family of transcription factors in Arabidopsis.

The TCP transcription factors control multiple developmental traits in diverse plant species. Members of this family share an approximately 60-residue-long TCP domain that binds to DNA. The TCP domain is predicted to form a basic helix-loop-helix (bHLH) structure but shares little sequence similarity with canonical bHLH domain. This classifies the TCP domain as a novel class of DNA binding domain specific to the plant kingdom. Little is known about how the TCP domain interacts with its target DNA. We report biochemical characterization and DNA binding properties of a TCP member in Arabidopsis thaliana, TCP4. We have shown that the 58-residue domain of TCP4 is essential and sufficient for binding to DNA and possesses DNA binding parameters comparable to canonical bHLH proteins. Using a yeast-based random mutagenesis screen and site-directed mutants, we identified the residues important for DNA binding and dimer formation. Mutants defective in binding and dimerization failed to rescue the phenotype of an Arabidopsis line lacking the endogenous TCP4 activity. By combining structure prediction, functional characterization of the mutants, and molecular modeling, we suggest a possible DNA binding mechanism for this class of transcription factors.

Effect of particle shape on capillary forces acting on particles at the air-water interface.

The capillary forces exerted by moving air-water interfaces can dislodge particles from stationary surfaces. The magnitude of the capillary forces depends on particle shape, orientation, and surface properties, such as contact angle and roughness. The objective was to quantify, both experimentally and theoretically, capillary force variations as an air-water interface moves over the particles. We measured capillary forces as a function of position, i.e., force-position curves, on particles of different shape by using force tensiometry. The particles (5 mm nominal size) were made of polyacrylate and were fabricated using a 3D printer. Experimental measurements were compared with theoretical calculations. We found that force-position curves could be classified into in three categories according to particle shapes: (1) curves for particles with round cross sections, such as spheroidal particles, (2) curves for particles with fixed cross sections, such cylindrical or cubical particles, and (3) curves for particles with tapering cross sections, such as prismatic or tetrahedral particles. Spheroidal particles showed a continuously varying capillary force. Cylindrical or cubical particles showed pronounced pinning of the air-water interface line at edges. The pinning led to an increased capillary force, which was relaxed when the interface snapped off from the edges. Particles with tapering cross section did not show pinning and showed reduced capillary forces as the air-water interface line perimeter and displacement cross section continuously decrease when the air-water interface moved over the particles.

Capillary forces between sediment particles and an air-water interface.

In the vadose zone, air-water interfaces play an important role in particle fate and transport, as particles can attach to the air-water interfaces by action of capillary forces. This attachment can either retard or enhance the movement of particles, depending on whether the air-water interfaces are stationary or mobile. Here we use three standard PTFE particles (sphere, circular cylinder, and tent) and seven natural mineral particles (basalt, granite, hematite, magnetite, mica, milky quartz, and clear quartz) to quantify the capillary forces between an air-water interface and the different particles. Capillary forces were determined experimentally using tensiometry, and theoretically assuming volume-equivalent spherical, ellipsoidal, and circular cylinder shapes. We experimentally distinguished between the maximum capillary force and the snap-off force when the air-water interface detaches from the particle. Theoretical and experimental values of capillary forces were of similar order of magnitude. The sphere gave the smallest theoretical capillary force, and the circular cylinder had the largest force due to pinning of the air-water interface. Pinning was less pronounced for natural particles when compared to the circular cylinder. Ellipsoids gave the best agreement with measured forces, suggesting that this shape can provide a reasonable estimation of capillary forces for many natural particles.

Current scenario on adhesion to zirconia; surface pretreatments and resin cements: A systematic review.

Several methods have been proposed to increase bonding of zirconia with resin. However, we are still to find the Holy Grail. A systematic literature review was performed through PubMed on international literature from January 2000 to May 2021 with relevant Medical Subject Headings terms. 56 articles were found to be relevant. Of all the different methods proposed, mechanochemical pretreatment of zirconia surface with alumina oxide and use of 10-methacryloyloxydecyl dihydrogen phosphate were found to be most effective as per majority of studies. New methods that require further research also surfaced.

What fuels the fly: Energy metabolism in Drosophila and its application to the study of obesity and diabetes.

The organs and metabolic pathways involved in energy metabolism, and the process of ATP production from nutrients, are comparable between humans and Drosophila melanogaster This level of conservation, together with the power of Drosophila genetics, makes the fly a very useful model system to study energy homeostasis. Here, we discuss the major organs involved in energy metabolism in Drosophila and how they metabolize different dietary nutrients to generate adenosine triphosphate. Energy metabolism in these organs is controlled by cell-intrinsic, paracrine, and endocrine signals that are similar between Drosophila and mammals. We describe how these signaling pathways are regulated by several physiological and environmental cues to accommodate tissue-, age-, and environment-specific differences in energy demand. Last, we discuss several genetic and diet-induced fly models of obesity and diabetes that can be leveraged to better understand the molecular basis of these metabolic diseases and thereby promote the development of novel therapies.

Effect of structural modifications on the spectroscopic properties and dynamics of the excited states of peridinin.

The spectroscopic properties and dynamics of the lowest excited singlet states of peridinin and two derivatives have been studied by steady-state absorption and fast-transient optical spectroscopic techniques. One derivative denoted PerOlEs, possesses a double bond and a methyl ester group instead of the r-ylidenebutenolide of peridinin. Another derivative denoted PerAcEs, is the biosynthetic precursor of peridinin and possesses a triple bond and a methyl ester group corresponding to the r-ylidenbutenolide function. Ultrafast time-resolved spectroscopic experiments in the visible and near-infrared regions were performed on the molecules and reveal the energies and regarding the structural features and interactions responsible for the unusual solvent-induced changes in the steady-state and transient absorption spectra and dynamics of dynamics of the excited electronic states. The data also provide information peridinin.

An Evolutionarily Conserved uORF Regulates PGC1α and Oxidative Metabolism in Mice, Flies, and Bluefin Tuna.

Mitochondrial abundance and function are tightly controlled during metabolic adaptation but dysregulated in pathological states such as diabetes, neurodegeneration, cancer, and kidney disease. We show here that translation of PGC1α, a key governor of mitochondrial biogenesis and oxidative metabolism, is negatively regulated by an upstream open reading frame (uORF) in the 5' untranslated region of its gene (PPARGC1A). We find that uORF-mediated translational repression is a feature of PPARGC1A orthologs from human to fly. Strikingly, whereas multiple inhibitory uORFs are broadly present in fish PPARGC1A orthologs, they are completely absent in the Atlantic bluefin tuna, an animal with exceptionally high mitochondrial content. In mice, an engineered mutation disrupting the PPARGC1A uORF increases PGC1α protein levels and oxidative metabolism and confers protection from acute kidney injury. These studies identify a translational regulatory element governing oxidative metabolism and highlight its potential contribution to the evolution of organismal mitochondrial function.

Effect of pi-electron conjugation length on the solvent-dependent S(1) lifetime of peridinin.

Peridinin exhibits an anomalous solvent dependence of its S(1) excited state lifetime attributed to the presence of an intramolecular charge transfer (ICT) state. The nature of this state has yet to be elucidated. Ultrafast time-resolved optical spectroscopy has been performed on a synthetic analog, C(35)-peridinin, having one less conjugated double bond than peridinin. The data reveal the lifetime decreases from 1.5 ns in n-hexane to 9.2 ps in methanol, an order of magnitude larger than peridinin. This is the strongest solvent dependence on the lifetime of an S(1) state of a carotenoid yet reported. The data support the view that the S(1) and ICT states are strongly coupled.

Thermogenesis by THADA.

THADA has been associated with cold adaptation and diabetes in humans, but the cellular and molecular basis of its function has been unknown. Moraru and colleagues (2017) report in this issue of Developmental Cell that it triggers thermogenesis by uncoupling ATP hydrolysis from calcium transport into the endoplasmic reticulum.

Cdk12 Is A Gene-Selective RNA Polymerase II Kinase That Regulates a Subset of the Transcriptome, Including Nrf2 Target Genes.

The Nrf2 transcription factor is well conserved throughout metazoan evolution and serves as a central regulator of adaptive cellular responses to oxidative stress. We carried out an RNAi screen in Drosophila S2 cells to better understand the regulatory mechanisms governing Nrf2 target gene expression. This paper describes the identification and characterization of the RNA polymerase II (Pol II) kinase Cdk12 as a factor that is required for Nrf2 target gene expression in cell culture and in vivo. Cdk12 is, however, not essential for bulk mRNA transcription and cells lacking CDK12 function are viable and able to proliferate. Consistent with previous findings on the DNA damage and heat shock responses, it emerges that Cdk12 may be specifically required for stress activated gene expression. Transcriptome analysis revealed that antioxidant gene expression is compromised in flies with reduced Cdk12 function, which makes them oxidative stress sensitive. In addition to supporting Reactive Oxygen Species (ROS) induced gene activation, Cdk12 suppresses genes that support metabolic functions in stressed conditions. We suggest that Cdk12 acts as a gene-selective Pol II kinase that engages a global shift in gene expression to switch cells from a metabolically active state to "stress-defence mode" when challenged by external stress.

A versatile ΦC31 based reporter system for measuring AP-1 and Nrf2 signaling in Drosophila and in tissue culture.

This paper describes the construction and characterization of a system of transcriptional reporter genes for monitoring the activity of signaling pathways and gene regulation mechanisms in intact Drosophila, dissected tissues or cultured cells. Transgenic integration of the reporters into the Drosophila germline was performed in a site-directed manner, using ΦC31 integrase. This strategy avoids variable position effects and assures low base level activity and high signal responsiveness. Defined integration sites furthermore enable the experimenter to compare the activity of different reporters in one organism. The reporter constructs have a modular design to facilitate the combination of promoter elements (synthetic transcription factor binding sites or natural regulatory sequences), reporter genes (eGFP, or DsRed.T4), and genomic integration sites. The system was used to analyze and compare the activity and signal response profiles of two stress inducible transcription factors, AP-1 and Nrf2. To complement the transgenic reporter fly lines, tissue culture assays were developed in which the same synthetic ARE and TRE elements control the expression of firefly luciferase.

A Study on Effect of Surface Treatments on the Shear Bond Strength between Composite Resin and Acrylic Resin Denture Teeth.

Visible light-cured composite resins have become popular in prosthetic dentistry for the replacement of fractured/debonded denture teeth, making composite denture teeth on partial denture metal frameworks, esthetic modification of denture teeth to harmonize with the characteristics of adjacent natural teeth, remodelling of worn occlusal surfaces of posterior denture teeth etc. However, the researches published on the bond strength between VLC composite resins and acrylic resin denture teeth is very limited. The purpose of this study is to investigate the effect of five different methods of surface treatments on acrylic resin teeth on the shear bond strength between light activated composite resin and acrylic resin denture teeth. Ninety cylindrical sticks of acrylic resin with denture teeth mounted atop were prepared. Various treatments were done upon the acrylic resin teeth surfaces. The samples were divided into six groups, containing 15 samples each. Over all the treated and untreated surfaces of all groups, light-cured composite resin was applied. The shear strengths were measured in a Universal Testing Machine using a knife-edge shear test. Data were analyzed using one way analysis of variance (ANOVA) and mean values were compared by the F test. Application of bonding agent with prior treatment of methyl methacrylate on the acrylic resin denture teeth resulted in maximum bond strength with composite resin.

Spectroscopic investigation of peridinin analogues having different pi-electron conjugated chain lengths: exploring the nature of the intramolecular charge transfer state.

The lifetime of the lowest excited singlet (S(1)) state of peridinin and many other carbonyl-containing carotenoids and polyenes has been reported to depend on the polarity of the solvent. This effect has been attributed to the presence of an intramolecular charge transfer (ICT) state in the manifold of excited states for these molecules. The nature of this ICT state has yet to be elucidated. In the present work, steady-state and ultrafast time-resolved optical spectroscopy have been performed on peridinin and three synthetic analogues, C(33)-peridinin, C(35)-peridinin, and C(39)-peridinin, which have different numbers of conjugated carbon-carbon double bonds. Otherwise, the molecules are structurally similar in that they possess the same functional groups. The trends in the positions of the steady-state and transient spectral profiles for this systematic series of molecules allow an assignment of the spectral features to transitions involving the S(0), S(1), S(2), and ICT states. A kinetics analysis reveals the lifetimes of the excited states and the dynamics of their excited state deactivation pathways. The most striking observation in the data is that the lifetime of the ICT state converges to the same value of 10.0 +/- 2.0 ps in the polar solvent, methanol, for all the peridinin analogues, regardless of the extent of pi-electron conjugation. This suggests that the ICT state is highly localized on the lactone ring, which is a common structural feature in all the molecules. The data further suggest that the S(1) and ICT states behave independently and that the ICT state is populated from both S(1) and S(2), the rate and efficiency from S(1) being dependent on the length of the pi-electron chain of the carotenoid and the solvent polarity.