Understanding cancer stem cells and plasticity: Towards better therapeutics.

The ability of cancer cells to finally overcome various lines of treatment in due course has always baffled the scientific community. Even with the most promising therapies, relapse is ultimately seen, and this resilience has proved to be a major hurdle in the management of cancer. Accumulating evidence now attributes this resilience to plasticity. Plasticity is the ability of cells to change their properties and is substantial as it helps in normal tissue regeneration or post-injury repair processes. It also helps in the overall maintenance of homeostasis. Unfortunately, this critical ability of cells, when activated incorrectly, can lead to numerous diseases, including cancer. Therefore, in this review, we focus on the plasticity aspect with an emphasis on cancer stem cells (CSCs). We discuss the various forms of plasticity that provide survival advantages to CSCs. Moreover, we explore various factors that affect plasticity. Furthermore, we provide the therapeutic implications of plasticity. Finally, we provide an insight into the future targeted therapies involving plasticity for better clinical outcomes.

House-warming: Wild king cobra nests have thermal regimes that positively affect hatching success and hatchling size.

Incubation temperature in nests of oviparous reptiles affects reproductive success indicators, including hatching time and success, offspring size, fitness, and behaviour. The female king cobra builds an above ground nest to incubate and protect its eggs. However, it is not clear how thermal regimes inside king cobra nests respond to external environmental temperature regimes, especially in subtropical regions that witness high diel and seasonal temperature fluctuations. To better understand the relationship between inside nest temperatures and hatching outcomes for this snake, we monitored the thermal regimes of 25 natural king cobra nests in the subtropical forests of the Western Himalayas in Uttarakhand state, northern India. We hypothesized that inside nest temperatures would be higher than outside (ambient) temperatures and that thermal regimes inside nests would affect hatching success and hatchling size. Internal and external temperatures at nest sites were measured every hour until hatching, via automatic data loggers. We then calculated hatching success of eggs and measured hatchling length and weight. Mean inside nest temperatures were consistently higher by about 3.0 °C than outside environmental temperatures. External temperature reduced with increasing elevation of nest sites and was the best determinant of inside nest temperature, which had a smaller range of variability. Physical characteristics of nests (size and leaf materials used) did not influence nest temperature significantly, but nest size was positively related to clutch size. Mean inside nest temperature was the best predictor of hatching success. Average daily minimum nest temperature, which indicates a possible lower threshold for thermal tolerance by eggs, was also correlated positively with hatching success. Mean daily maximum temperature was a significant predictor of mean length of hatchlings, but not of mean hatchling weight. Our study provides unequivocal evidence for the critical thermal benefits of king cobra nests for increased reproductive success, in subtropical environments with lower and sharply fluctuating temperature regimes.

Review on the extraction of calcium supplements from eggshells to combat waste generation and chronic calcium deficiency.

When faced with a plethora of issues, the possibility of one problem becoming the solution of another is a rare, yet beneficial scenario. This report explores the prospect of viewing the accumulation of organic waste matter in India as a potential calcium reservoir to relieve the issue of calcium deficiency in the population. Waste generation has seen gradual growth, and it has created a problem of waste disposal. A large segment of the generated waste primarily consists of food waste which contains significant amounts of nutrients. Food waste such as eggshells, waste from shellfish, bones, and fish scales contain good amounts of bioavailable calcium, and large quantities of this discarded bioavailable calcium remain unused. Global studies show India to have significantly lower levels of calcium intake than the global average, thus increasing the risk of calcium deficiency-related diseases. Furthermore, research shows that for over the past half of the century, the intake of dietary calcium has declined drastically throughout India. This has led to chronic calcium deficiency-related diseases throughout most of the Indian population. Hence, development of calcium supplements from calcium-rich waste material has the potential to not only reduce the strain on waste management, but also to provide the calcium-deficient population with a cheaper alternative to traditional supplements. Owing to the abundance and ease of separation, eggshells have been chosen as the focus of the review. This review highlights and compares their extraction methods of providing cheap calcium supplements while reducing the amount of eggshell waste.

Interacting effects of vessel noise and shallow river depth elevate metabolic stress in Ganges river dolphins.

In riverine 'soundscapes', complex interactions between sound, substrate type, and depth create difficulties in assessing impacts of anthropogenic noise pollution on freshwater fauna. Underwater noise from vessels can negatively affect endangered Ganges river dolphins (Platanista gangetica), which are 'almost blind' and rely entirely on high-frequency echolocation clicks to sense their environment. We conducted field-based acoustic recordings and modelling to assess acoustic responses of Platanista to underwater noise exposure from vessels in the Ganga River (India), which is now being transformed into a major waterway. Dolphins showed enhanced activity during acute noise exposure and suppressed activity during chronic exposure. Increase in ambient noise levels altered dolphin acoustic responses, strongly masked echolocation clicks, and more than doubled metabolic stress. Noise impacts were further aggravated during dry-season river depth reduction. Maintaining ecological flows, downscaling of vessel traffic, and propeller modifications to reduce cavitation noise, could help mitigate noise impacts on Ganges river dolphins.

Cutaneous nodules in Irrawaddy dolphins: an emerging disease in vulnerable populations.

The presence of cutaneous nodules is reported in vulnerable populations of Irrawaddy dolphins Orcaella brevirostris from Malaysia (Kuching, Bintulu-Similajau, Kinabatangan-Segama and Penang Island), India (Chilika Lagoon) and Bangladesh (Sundarbans). Approximately 5700 images taken for photo-identification studies in 2004 to 2013 were examined for skin disorders. Nodules were detected in 6 populations. They appeared as circumscribed elevations of the skin and varied in size from 2 to >30 mm, were sparse or numerous and occurred on all visible body areas. In 8 photo-identified (PI) dolphins from India and Malaysia, the lesions remained stable (N = 2) or progressed (N = 6) over months but did not regress. The 2 most severely affected individuals were seen in Kuching and the Chilika Lagoon. Their fate is unknown. Cutaneous nodules were sampled in a female that died in a gillnet in Kuching in 2012. Histologically, the lesions consisted of thick collagen bundles covered by a moderately hyperplasic epithelium and were diagnosed as fibropapillomas. Whether the nodules observed in the other O. brevirostris were also fibropapillomas remains to be investigated. Disease prevalence ranged from 2.2% (N = 46; Bintulu-Similajau) to 13.9% (N = 72; Chilika) in 4 populations from Malaysia and India. It was not significantly different in 3 study areas in eastern Malaysia. In Chilika, prevalence was significantly higher (p = 0.00078) in 2009 to 2011 (13.9%) than in 2004 to 2006 (2.8%) in 72 PI dolphins. The emergence of a novel disease in vulnerable O. brevirostris populations is of concern.

Long-term occupancy trends in a data-poor dugong population in the Andaman and Nicobar archipelago.

Prioritizing efforts for conserving rare and threatened species with limited past data and lacking population estimates is predicated on robust assessments of their occupancy rates. This is particularly challenging for elusive, long-lived and wide-ranging marine mammals. In this paper we estimate trends in long-term (over 50 years) occupancy, persistence and extinction of a vulnerable and data-poor dugong (Dugong dugon) population across multiple seagrass meadows in the Andaman and Nicobar archipelago (India). For this we use hierarchical Bayesian dynamic occupancy models accounting for false negatives (detection probability<1), persistence and extinction, to two datasets: a) fragmentary long-term occurrence records from multiple sources (1959-2004, n = 40 locations), and b) systematic detection/non-detection data from current surveys (2010-2012, n = 57). Dugong occupancy across the archipelago declined by 60% (from 0.45 to 0.18) over the last 20 years and present distribution was largely restricted to sheltered bays and channels with seagrass meadows dominated by Halophila and Halodule sp. Dugongs were not found in patchy meadows with low seagrass cover. In general, seagrass habitat availability was not limiting for dugong occupancy, suggesting that anthropogenic factors such as entanglement in gillnets and direct hunting may have led to local extinction of dugongs from locations where extensive seagrass meadows still thrive. Effective management of these remnant dugong populations will require a multi-pronged approach, involving 1) protection of areas where dugongs still persist, 2) monitoring of seagrass habitats that dugongs could recolonize, 3) reducing gillnet use in areas used by dugongs, and 4) engaging with indigenous/settler communities to reduce impacts of hunting.

Coexistence of fisheries with river dolphin conservation.

Freshwater biodiversity conservation is generally perceived to conflict with human use and extraction (e.g., fisheries). Overexploited fisheries upset the balance between local economic needs and endangered species' conservation. We investigated resource competition between fisheries and Ganges river dolphins (Platanista gangetica gangetica) in a human-dominated river system in India to assess the potential for their coexistence. We surveyed a 65-km stretch of the lower Ganga River to assess habitat use by dolphins (encounter rates) and fishing activity (habitat preferences of fishers, intensity of net and boat use). Dolphin abundance in the main channel increased from 179 (SE 7) (mid dry season) to 270 (SE 8) (peak dry season), probably as a result of immigration from upstream tributaries. Dolphins preferred river channels with muddy, rocky substrates, and deep midchannel waters. These areas overlapped considerably with fishing areas. Sites with 2-6 boats/km (moderately fished) were more preferred by dolphins than sites with 8-55 boats/km (heavily fished). Estimated spatial (85%) and prey-resource overlap (75%) between fisheries and dolphins (chiefly predators of small fish) suggests a high level of competition between the two groups. A decrease in abundance of larger fish, indicated by the fact that small fish comprised 74% of the total caught, may have intensified the present competition. Dolphins seem resilient to changes in fish community structure and may persist in overfished rivers. Regulated fishing in dolphin hotspots and maintenance of adequate dry season flows can sustain dolphins in tributaries and reduce competition in the main river. Fish-stock restoration and management, effective monitoring, curbing destructive fishing practices, secure tenure rights, and provision of alternative livelihoods for fishers may help reconcile conservation and local needs in overexploited river systems.