Marine estuaries act as better sink for greenhouse gases during winter in undisturbed mangrove than degraded ones in Sundarban, India.

The estuaries provide the key pathway for travelling carbon across the land-ocean interfaces and behave as both source and sink of greenhouse gases (GHGs) in water-atmosphere systems. The sink-source characteristics of estuaries for GHGs vary spatially. The primary driving factors are adjacent ecologies (agriculture, aquaculture, etc.) and proximities to the sea. To study the sink-source characteristics of estuaries for GHGs (methane (CH4), nitrous oxide (N2O) and carbon dioxide (CO2)), the water samples were collected from 53 different locations in the estuaries for estimation of dissolved GHGs concentration and air-water GHGs exchanges. The locations represent five zones (Zone I, II, III, IV and V) based on the type and degradation status of mangroves (degraded and undisturbed), anthropogenic activities, and distance from the sea. Zone I, III, V represents to the degraded mangroves far from sea, whereas, Zone II, IV surrounded by undisturbed mangroves and nearer to sea. The average dissolved CH4 concentrations were higher in the estuaries which were adjacent to degraded mangroves (154.4 nmol L-1) than undisturbed mangroves (81.7 nmol L-1). Further, the average dissolved N2O concentrations were 48% higher in the estuaries nearer to degraded mangroves than that of undisturbed ones. Among the degraded mangrove sites, the dissolved CO2 concentrations were higher at Zone I (30.1 µmol L-1) followed by Zone III and IV, whereas in undisturbed sites, it was higher in Zone IV (22.3 µmol L-1) than Zone II (17.6 µmol L-1). Among the 53 locations, 36, 51 and 33 locations acted as a sink (negative value of exchanges) for CH4, N2O and CO2, respectively. The higher sink potential for CH4 was recorded to those estuaries adjacent to undisturbed mangroves (-791.69 µmol m-2 d-1) than the degraded ones (-23.18 µmol m-2 d-1). Similarly, the average air-water N2O and CO2 exchanges were more negative in the estuaries which were nearer to undisturbed mangroves indicating higher sink potential. The pH, and salinity of the estuary water were negatively correlated with air-water CH4 and N2O exchanges, whereas those were positively correlated with CO2 exchanges. Significantly lower dissolved GHGs and air-water GHGs exchange was observed in the estuaries adjacent to the undisturbed mangrove as compared to the degraded mangrove. The reason behind higher sink behaviours of estuaries nearer to undisturbed mangroves are higher intrusion of seawater, less nutrient availability, higher salinity, low carbon contents and alkaline pH compared to estuaries adjacent to degraded mangroves and far from sea.

Assessment of urban growth effects on green space and surface temperature in Doon Valley, Uttarakhand, India.

This study aims to examine the spatio-temporal urban expansion pattern and its impacts on green space variation as well as thermal behavior in Doon valley over the last two decades during 2000 and 2019. Landsat 5 and Landsat 8 images of February and May month of two study years 2000 and 2019 were used for the analysis. The land use change analysis revealed notable outgrowth of urbanization with 184% increase in Doon valley during 2000-2019. To examine the effects of locational factors on urban growth, relative Shannon entropy analysis was carried out based on two factors, i.e., distances from city center and roads. It was seen that all the roads and city center have witnessed consistent and higher urban spread in its surroundings with high relative entropy value more than 0.9. Further analysis shows that there was considerable loss of agriculture crop lands and fallow lands along the major roads and around city center. Forest area was mostly affected along the road towards Mussorie hill station (road 2) because of its hilly surroundings whereas in Subhash Nagar area (road 4), fallow land and cultivated land were mainly replaced by the development activities. Analysis was also carried out to assess the spatial-temporal distribution of land surface temperature (LST) and its changing dynamics with land covers. It revealed that LST has increased in all the land use types with overall increase of 1.86 °C and 8.62 °C in the months February and May, respectively, during the study period. It is also found that normalized difference vegetation index (NDVI) and LST are negatively correlated with R2 0.46 and 0.28 for the months February and May, respectively. However, the correlation between NDVI and LST was found highly significant with P value less than 0.01. Therefore, spatial and temporal changes of different land use types especially rapid urbanization at the cost of green spaces with rampant anthropogenic activities is one of the main factor for LST increase in the study area. Moreover, this temperature rise with ever-increasing anthropogenic activities is not a healthy indication for the hilly region like Doon Valley which may adversely affect the ecosystem stability and its resources as well. The study may be used as reference for future ecological and urban management studies and policies.

Discovery of Potent and Selective Non-Nucleotide Small Molecule Inhibitors of CD73.

CD73 is an extracellular mediator of purinergic signaling. When upregulated in the tumor microenvironment, CD73 has been implicated in the inhibition of immune function through overproduction of adenosine. Traditional efforts to inhibit CD73 have involved antibody therapy or the development of small molecules, the most potent of which mimic the acidic and ionizable structure of the enzyme's natural substrate, adenosine 5'-monophosphate (AMP). Here, we report the systematic discovery of a novel class of non-nucleotide CD73 inhibitors that are more potent than all other nonphosphonate inhibitor classes reported to date. These efforts have culminated in the discovery of 4-({5-[4-fluoro-1-(2H-indazol-6-yl)-1H-1,2,3-benzotriazol-6-yl]-1H-pyrazol-1-yl}methyl)benzonitrile (73, IC50 = 12 nM) and 4-({5-[4-chloro-1-(2H-indazol-6-yl)-1H-1,2,3-benzotriazol-6-yl]-1H-pyrazol-1-yl}methyl)benzonitrile (74, IC50 = 19 nM). Cocrystallization of 74 with human CD73 demonstrates a competitive binding mode. These compounds show promise for the improvement of drug-like character via the attenuation of the acidity and low membrane permeability inherent to known nucleoside inhibitors of CD73.

18F-Deoxyfluorination of Phenols via Ru π-Complexes.

The deficiency of robust and practical methods for 18F-radiofluorination is a bottleneck for positron emission tomography (PET) tracer development. Here, we report the first transition-metal-assisted 18F-deoxyfluorination of phenols. The transformation benefits from readily available phenols as starting materials, tolerance of moisture and ambient atmosphere, large substrate scope, and translatability to generate doses appropriate for PET imaging.

Streamlined Total Synthesis of Uncialamycin and Its Application to the Synthesis of Designed Analogues for Biological Investigations.

From the enediyne class of antitumor antibiotics, uncialamycin is among the rarest and most potent, yet one of the structurally simpler, making it attractive for chemical synthesis and potential applications in biology and medicine. In this article we describe a streamlined and practical enantioselective total synthesis of uncialamycin that is amenable to the synthesis of novel analogues and renders the natural product readily available for biological and drug development studies. Starting from hydroxy- or methoxyisatin, the synthesis features a Noyori enantioselective reduction, a Yamaguchi acetylide-pyridinium coupling, a stereoselective acetylide-aldehyde cyclization, and a newly developed annulation reaction that allows efficient coupling of a cyanophthalide and a p-methoxy semiquinone aminal to forge the anthraquinone moiety of the molecule. Overall, the developed streamlined synthesis proceeds in 22 linear steps (14 chromatographic separations) and 11% overall yield. The developed synthetic strategies and technologies were applied to the synthesis of a series of designed uncialamycin analogues equipped with suitable functional groups for conjugation to antibodies and other delivery systems. Biological evaluation of a select number of these analogues led to the identification of compounds with low picomolar potencies against certain cancer cell lines. These compounds and others like them may serve as powerful payloads for the development of antibody drug conjugates (ADCs) intended for personalized targeted cancer therapy.

Total Synthesis and Biological Evaluation of Natural and Designed Tubulysins.

A streamlined total synthesis of N(14)-desacetoxytubulysin H (Tb1) based on a C-H activation strategy and a short total synthesis of pretubulysin D (PTb-D43) are described. Applications of the developed synthetic strategies and technologies to the synthesis of a series of tubulysin analogues (Tb2-Tb41 and PTb-D42) are also reported. Biological evaluation of the synthesized compounds against an array of cancer cells revealed a number of novel analogues (e.g., Tb14), some with exceptional potencies against certain cell lines [e.g., Tb32 with IC50 = 12 pM against MES SA (uterine sarcoma) cell line and 2 pM against HEK 293T (human embryonic kidney) cell line], and a set of valuable structure-activity relationships. The highly potent cytotoxic compounds discovered in this study are highly desirable as payloads for antibody-drug conjugates and other drug delivery systems for personalized targeted cancer chemotherapies.

Comparing risk behaviours of human papillomavirus-vaccinated and non-vaccinated women.

BACKGROUND: Since September 2008, a national vaccine programme in the UK has offered routine human papillomavirus (HPV) vaccination to young women aged 12-13 years. A catch-up programme also offered HPV vaccination to women born after 1 September 1990. AIM: To compare indicators of risk and preventive behaviours among young women attending genitourinary medicine (GUM) clinics who had, and had not, received at least one dose of HPV vaccine. METHODS: Clinical histories and HPV vaccination status were obtained from 363 participants eligible for HPV vaccination (Cervarix(®)) in the UK vaccination programme (born after 1 September 1990) attending GUM clinics in the North West of England. Using logistic regression, markers of sexual and non-sexual risk behaviours were compared between vaccinated and unvaccinated women. RESULTS: At least one dose of HPV vaccine had been received by 63.6% (n=231) of participants. Unvaccinated women demonstrated higher levels of risky behaviour than those who had undergone HPV vaccination. Unvaccinated women were significantly more likely to have had three or more partners in the last 6 months, attended the clinic with symptoms, not used a condom at first sexual intercourse, had anal intercourse with their last sexual contact, to have tested positive for Chlamydia trachomatis diagnosis at the clinic visit and to be a current smoker. CONCLUSIONS: In the UK, where vaccine coverage is high, failure to initiate HPV vaccination amongst GUM attendees is a marker of high-risk behaviours. As a result, HPV vaccination status should be ascertained as part of an individual's clinical history by sexual health services to ensure advice and counselling is provided to those at greatest risk of HPV-associated disease.

Identification of soil erosion risk areas for conservation planning in different states of India.

Assessment of soil erosion risks, especially in the developing countries, is a challenging task mainly due to non-availability or insufficiency of relevant data. In this paper, the soil erosion risks have been estimated by integrating the spatial data on potential erosion rates and soil loss tolerance limits for conservation planning at state level in India. The erosion risk classes have been prioritized based upon the difference between the prevailing erosion rates and the permissible erosion limits. The analysis revealed that about 50% of total geographical area (TGA) of India, falling in five priority erosion risk classes, requires different intensity of conservation measures though about 91% area suffers from potential erosion rates varying from < 5 to > 40 t ha(-1) yr(-1). Statewise analysis indicated that Andhra Pradesh, Maharashtra and Rajasthan share about 75% of total area under priority Class 1 (6.4 M ha) though they account for only 19.4% of the total area (36.2 M ha) under very severe potential erosion rate category (> 40 t ha(-1)yr(-1)). It was observed that about 75% of total geographical area (TGA) in the states of Bihar, Gujarat, Haryana, Kerala and Punjab does not require any specific soil conservation measure as the potential erosion rates are well within the tolerance limits. The developed methodology can be successfully employed for prioritization of erosion risk areas at watershed, region or country level.

Synthesis of dragmacidin D via direct C-H couplings.

Dragmacidin D, an emerging biologically active marine natural product, has attracted attention as a lead compound for treating Parkinson's and Alzheimer's diseases. Prominent structural features of this compound are the two indole-pyrazinone bonds and the presence of a polar aminoimidazole unit. We have established a concise total synthesis of dragmacidin D using direct C-H coupling reactions. Methodological developments include (i) Pd-catalyzed thiophene-indole C-H/C-I coupling, (ii) Pd-catalyzed indole-pyrazine N-oxide C-H/C-H coupling, and (iii) acid-catalyzed indole-pyrazinone C-H/C-H coupling. These regioselective catalytic C-H couplings enabled us to rapidly assemble simple building blocks to construct the core structure of dragmacidin D in a step-economical fashion.

Stroke in pregnancy associated with syphilis.

The Incidence of Syphilis has increased in developed countries over recent years. This potentially could lead to a rise in the number of cases presenting in obstetrics and a resurgence of congenital syphilis. Syphilis is a treatable condition, screening in pregnancy is both cost effective and cost beneficial. We describe a rare presentation of syphilis in a young woman in early pregnancy. The patient presented with a stroke, at which time her partner was diagnosed with early latent syphilis. Her findings were thought to be consistent with meningovascular syphilis and treatment lead to resolution of her symptoms. Antenatal screening for syphilis is offered to all women in the UK. Changing migration patterns and high-risk behavior however, may cause cases to go undetected. Vigilant screening for syphilis is needed in pregnancy as prompt diagnosis and management will aim to cure the mother whilst preventing the adverse effects associated with congenital syphilis.

Intravaginal clindamycin to reduce preterm birth in women with abnormal genital tract flora.

OBJECTIVE: To assess the ability of clindamycin vaginal cream to reduce the incidence of preterm birth in women with abnormal genital tract flora in the second trimester of pregnancy. METHODS: This was a randomized, double-blind, placebo-controlled, tricenter study. A total of 409 women with abnormal genital tract flora on Gram stain of vaginal secretions at 13-20 weeks' gestation were randomized to receive a 3-day course of clindamycin vaginal cream or placebo. Those women who still had abnormal vaginal flora 3 weeks later received a 7-day course of the original study drug (ie, either clindamycin vaginal cream or placebo as per original randomization). The primary outcome measure was the incidence of preterm birth. RESULTS: There was a statistically significant reduction in the incidence of preterm birth in the clindamycin vaginal cream group (4%) compared with placebo (10%) (P <.03). Significantly more babies born preterm (63%) required admission to the neonatal intensive care unit compared with term infants (4%) (P <.001). CONCLUSION: A 2% clindamycin vaginal cream, when compared with placebo administered to women with abnormal genital tract flora before 20 weeks' gestation, can reduce the incidence of preterm birth by 60% and hence the need for neonatal intensive care.

The efficacy of vaginal clindamycin for the treatment of abnormal genital tract flora in pregnancy.

OBJECTIVE: To assess the efficacy of 2% clindamycin vaginal cream (CVC) to treat bacterial vaginosis (BV) in pregnancy. METHODS: A prospective, randomized, double-blind, placebo-controlled, tricenter study. Four hundred and four women with BV on Gram stain at their first antenatal clinic visit were randomized to receive a 3-day course of 2% CVC or placebo. The outcome was assessed using an intention to treat analysis at 3 weeks and 6 weeks post-treatment according to three different diagnostic methods based on five criteria (Gram stain and all four elements of clinical composite criteria: vaginal discharge, abnormal vaginal pH, clue cells, amine odor), three criteria (vaginal pH, clue cells, amine odor) or two criteria (clue cells and amine odor) to reflect stringency of diagnosis, historical precedence and government agency recommendations respectively. RESULTS: Using five diagnostic criteria, 18% of CVC patients were cured and 70.8% either cured and/or improved compared to 1.6% and 12% of placebo patients respectively (p < 0.0001). Using three diagnostic criteria, 44.8% of CVC patients were cured and 77.3% were either cured and/or improved compared to 9.3% and 28.8% of placebo patients respectively (p < 0.000 1). Using two diagnostic criteria, 75.0% of CVC patients were cured compared to 18.0% of placebo patients (p < 0.0001 ). Recurrence rates in those CVC patients successfully treated were approximately 6% at 6 weeks post baseline and 10% at 28 to 34 weeks gestation. CONCLUSIONS: A 3-day course of CVC appears to be well tolerated by the mother and statistically significantly more efficacious than placebo in the treatment of BV during the second trimester of pregnancy.