Self-Replication Without Hydrogen-Bonds: An Exobiotic Design.

Life on Earth uses DNA as the central template for self-replication, genetic encoding, and information transfer. However, there are no physical laws precluding life's existence elsewhere in space, and alternative life forms may not need DNA. In the search for exobiology, knowing what to look for as a biosignature remains a challenge-especially if it is not from the obvious list of biologic building blocks. Clues from chemicals recently discovered on Mars and in the Taurus Molecular Cloud 1 (TMC-1), show that intriguing organic compounds exist beyond Earth, which could provide a starting point for unconventional exobiotic designs. Here we present a new self-replicating system with structural similarities to recently discovered compounds on Mars and TMC-1. Rather than using DNA's hydrogen-bonding motif for reliable base-paring, our design employs sulfur-nitrogen interactions to selectively template unique benzothiadiazole units in sequence. We synthesized and studied two versions of this system, one reversible and the other irreversible, and found experimental evidence of self-replication in d-chloroform solvent. These results are part of a larger pursuit in our lab for developing a basis for a potential exobiological system using starting blocks closely related to these cosmic compounds.

Ajay Kumar Parida (1963-2022), an eminent plant biotechnologist with a passion for mangrove biology.

We remember Dr Ajay Parida, a leading plant biotechnologist, whose premature passing has deprived the Indian plant science community of a committed scientist and an able administrator. Born on 12 December 1963 in Bhagabanpur, Cuttack District (now Jajpur district), Odisha, he passed away in Guwahati on 19 July 2022. A collegial scientist, his down-to-earth and approachable nature, as well as his resourcefulness were instrumental in advancing the cause of Indian science and harnessing frontier biotechnological tools as vehicles of social consciousness. His expertise in quantitative DNA variation and molecular marker analysis, paved the way for subsequent research on mangrove molecular diversity at the M. S. Swaminathan Research Foundation (MSSRF), Chennai. His contributions to mangrove biology, genetics and genomics as well as extremophile plant species in the Indian context over two decades are a benchmark in his field. He also provided commendable leadership in his capacity as Director, Institute of Life Sciences (ILS), Bhubaneshwar during the COVID-19 pandemic.

Traditional uses, phytochemistry, pharmacology, and toxicology of the genus Artemisia L. (Asteraceae): A high-value medicinal plant.

Biologically active secondary metabolites, essential oils, and volatile compounds derived from medicinal and aromatic plants play a crucial role in promoting human health. Within the large family Asteraceae, the genus Artemisia consists of approximately 500 species. Artemisia species have a rich history in traditional medicine worldwide, offering remedies for a wide range of ailments, such as malaria, jaundice, toothache, gastrointestinal problems, wounds, inflammatory diseases, diarrhoea, menstrual pains, skin disorders, headache, and intestinal parasites. The therapeutic potential of Artemisia species is derived from a multitude of phytoconstituents, including terpenoids, phenols, flavonoids, coumarins, sesquiterpene lactones, lignans, and alkaloids that serve as active pharmaceutical ingredients (API). The remarkable antimalarial, antimicrobial, anthelmintic, antidiabetic, anti-inflammatory, anticancer, antispasmodic, antioxidative and insecticidal properties possessed by the species are attributed to these APIs. Interestingly, several commercially utilized pharmaceutical drugs, including arglabin, artemisinin, artemether, artesunate, santonin, and tarralin have also been derived from different Artemisia species. However, despite the vast medicinal potential, only a limited number of Artemisia species have been exploited commercially. Further, the available literature on traditional and pharmacological uses of Artemisia lacks comprehensive reviews. Therefore, there is an urgent need to bridge the existing knowledge gaps and provide a scientific foundation for future Artemisia research endeavours. It is in this context, the present review aims to provide a comprehensive account of the traditional uses, phytochemistry, documented biological properties and toxicity of all the species of Artemisia and offers useful insights for practitioners and researchers into underutilized species and their potential applications. This review aims to stimulate further exploration, experimentation and collaboration to fully realize the therapeutic potential of Artemisia in augmenting human health and well-being.

Allium cytogenetics: a critical review on the Indian taxa.

The genus Allium Linnaeus, 1753 (tribe Allieae) contains about 800 species worldwide of which almost 38 species are reported in India, including the globally important crops (onion, garlic, leek, shallot) and many wild species. A satisfactory chromosomal catalogue of Allium species is missing which has been considered in the review for the species occurring in India. The most prominent base number is x=8, with few records of x=7, 10, 11. The genome size has sufficient clues for divergence, ranging from 7.8 pg/1C to 30.0 pg/1C in diploid and 15.16 pg/1C to 41.78 pg/1C in polyploid species. Although the karyotypes are seemingly dominated by metacentrics, substantial variation in nucleolus organizing regions (NORs) is noteworthy. The chromosomal rearrangement between A.cepa Linnaeus, 1753 and its allied species has paved way to appreciate genomic evolution within Allium. The presence of a unique telomere sequence and its conservation in Allium sets this genus apart from all other Amaryllids and supports monophyletic origin. Any cytogenetic investigation regarding NOR variability, telomere sequence and genome size in the Indian species becomes the most promising field to decipher chromosome evolution against the background of species diversity and evolution, especially in the Indian subcontinent.

Telemedicine: Embracing virtual care during COVID-19 pandemic.

Telemedicine and related e-health facilities facilitate care from a distance through electronic information systems. COVID-19 pandemic is establishing telemedicine in the health care delivery system of countries. Telehealth is contributing significantly in health care delivery during the COVID-19 crisis. For mild-to-moderate symptoms of COVID-19 or any illness, telehealth services might represent a better, efficient way to receive initial care and perform triaging. Telemedicine also has a significant role in screening for COVID-19 symptoms and delivering routine needs and follow-up care. The large-scale adoption of telemedicine in public health care delivery is still not visible in low- and middle-income countries like India. Adoption by patients and healthcare professionals is limited and their concerns need to be addressed to ensure its utilization in future of the care continuum. In the current paper, we aim to review recent measures of Telemedicine adopted during the course of pandemic and its impact on public health in lower-middle income countries like India.

Long-term Survival Results following Endobronchial RF Ablation in a Healthy-Porcine Model.

This paper presents results from long-term survival study where healthy swine were ablated with a novel technology designed for treating early-stage non-small cell lung cancer using an endobronchial flexible catheter.Methods - The radiofrequency ablation (RFA) system has been presented previously and consisted of an ablation catheter, radiofrequency generator, irrigation pump for infusion of hypertonic saline (HS) and a laptop. The catheter carried an occlusion balloon, a 5 mm long RF electrode, with irrigation holes, and a 1 mm long electrode for bipolar impedance measurements. The outer diameter (OD) was 1.4 mm for compatibility with current bronchoscopes, navigation systems and radial EBUS. Nine swine were treated in this study with survival times of 1, 4 and 12 weeks (N=3 at each time point). In all animals, the treatment sites consisted of one location in the upper right lung (RUL) and another one in the lower right lung (RLL). CTs were taken pre-op, immediately post-op and at every 2 weeks post treatment. Ablation times ranged from 6 to 8 min and average applied power was 68 W (range 63 - 72 W).Results - At 1-week survival, large zones of necrotic tissue were observed in all respective 6 ablations. Ablation volumes had an average diameter of 3.2 cm at RUL locations and 3.8 cm in RLLs (likely due to longer RLL ablation durations). As time progressed, the necrotic tissue was gradually replaced with fibrotic tissue. At 4-week survival, the replacement was almost complete in all respective 3 animals. As a result, ablation volumes decreased to an average diameter of 1.3 cm at RUL locations and 2.3 cm in RLLs (likely due to longer RLL ablation durations). At 12-week survival, as the replacement process continued, histopathology revealed zones of residual necrotic tissue that were further reduced in size. Ablation zones had been resorbed and contracted by fibrous scar tissue. The average volume of the treatment effect decreased to 1.1 cm (RUL) and to 1.6 cm (RLL) in equivalent diameter. There were no complications in any of the nine animals.Conclusion - In healthy swine lungs, RFA with a 1.4-mm OD, radial-EBUS-sheath-compatible, endobronchial catheter was effective and safe. This system and therapeutic approach may be considered for further evaluation in minimally invasive treatment of tumorous lung nodules.

Changing the Nature of Quantitative Biology Education: Data Science as a Driver.

We live in a data-rich world with rapidly growing databases with zettabytes of data. Innovation, computation, and technological advances have now tremendously accelerated the pace of discovery, providing driverless cars, robotic devices, expert healthcare systems, precision medicine, and automated discovery to mention a few. Even though the definition of the term data science continues to evolve, the sweeping impact it has already produced on society is undeniable. We are at a point when new discoveries through data science have enormous potential to advance progress but also to be used maliciously, with harmful ethical and social consequences. Perhaps nowhere is this more clearly exemplified than in the biological and medical sciences. The confluence of (1) machine learning, (2) mathematical modeling, (3) computation/simulation, and (4) big data have moved us from the sequencing of genomes to gene editing and individualized medicine; yet, unsettled policies regarding data privacy and ethical norms could potentially open doors for serious negative repercussions. The data science revolution has amplified the urgent need for a paradigm shift in undergraduate biology education. It has reaffirmed that data science education interacts and enhances mathematical education in advancing quantitative conceptual and skill development for the new generation of biologists. These connections encourage us to strive to cultivate a broadly skilled workforce of technologically savvy problem-solvers, skilled at handling the unique challenges pertaining to biological data, and capable of collaborating across various disciplines in the sciences, the humanities, and the social sciences. To accomplish this, we suggest development of open curricula that extend beyond the job certification rhetoric and combine data acumen with modeling, experimental, and computational methods through engaging projects, while also providing awareness and deep exploration of their societal implications. This process would benefit from embracing the pedagogy of experiential learning and involve students in open-ended explorations derived from authentic inquiries and ongoing research. On this foundation, we encourage development of flexible data science initiatives for the education of life science undergraduates within and across existing models.

UPLC-DAD Assisted Phytochemical Quantitation Reveals a Sex, Ploidy and Ecogeography Specificity in the Expression Levels of Selected Secondary Metabolites in Medicinal Tinospora cordifolia: Implications for Elites' Identification Program.

BACKGROUND: Medicinal phytochemistry involving UPLC-DAD in an exhaustive analysis involving quantification of eight commercially important phytochemicals viz. syringin, cordifolioside A, magnoflorine, tinocordiside, palmatine, 20ß-hydroxyecdysone, L-tetrahydropalmatine and berberine has been done in 143 accessions from eight states and the union territories of Delhi and Jammu & Kashmir of India representing three different ploidy levels viz. diploid (2x), triploid (3x) and synthetic tetraploid (4x). The study was done to assess the effect of sex, ploidy level and ecogeography on the expression level of secondary metabolites in stems of dioecious, medicinally important shrub Tinospora cordifolia. METHODS: Two different UPLC-DAD methods were used for the quantification of eight selected phytochemicals from the alcoholic stem extracts of T. cordifolia accessions. The Waters Acquity UPLC system hyphenated to the QTOF micromass system, equipped with PDA and ESI-Q-TOF detectors was utilized for the quantitative analysis, Mass Lynx v 4.0 software was used for data analysis. RESULTS: Significant quantitative changes were observed in the analysed secondary metabolites among different accessions of T. cordifolia. The triploid (3x) cytotypes revealed higher amounts of seven out of eight analysed secondary metabolites than diploids and only 20ß-hydroxyecdysone was observed to be present in significantly higher amount in diploid cytotypes. Further, at the tetraploid level, novel induced colchiploid (synthetic 4x) genotypes revealed increase in the yield of all of the analysed eight phytochemicals than their respective diploid counterparts. The quantity of active principles in tetraploid cytotypes were also higher than the average triploid levels at multiple locations in five out of eight tested phytochemicals, indicating the influence of ploidy on expression levels of secondary metabolites in T. cordifolia. Additionally, at each of the three ploidy levels (2x, 3x and synthetic 4x), a significant sex specificity could be observed in the expression levels of active principles, with female sex outperforming the male in the content of some phytochemicals, while others getting overexpressed in the male sex. The manifestation of diverse ecogeographies on secondary metabolism was observed in the form of identification of high yielding accessions from the states of Madhya Pradesh, Delhi and Himachal Pradesh and the Union territory of Jammu & Kashmir. Two triploid female accessions that contained approximately two- to eight fold higher amounts of five out of the eight analysed phytochemicals have been identified as superior elites from the wild from the states of Delhi and Madhya Pradesh. CONCLUSION: The paper shows the first observations of ploidy specificity along with subtle sex and ecogeography influence on the expression levels of secondary metabolome in T. cordifolia.

Early Preclinical Experience with a Novel Endobronchial Radiofrequency Ablation System for Lung Cancer Treatment.

This paper introduces a novel technology for treating early-stage non-small cell lung cancer using an endobronchial approach via a flexible radiofrequency ablation (RFA) catheter. Methods - The RFA system consisted of an ablation catheter, radiofrequency generator, irrigation pump for infusion of hypertonic saline (HS) and a laptop. The catheter carried an occlusion balloon, a 5 mm long RF electrode, with irrigation holes, and a 1 mm long electrode for bipolar impedance measurements. The outer diameter was 1.4 mm for compatibility with current bronchoscopes, navigation systems and radial EBUS. The RFA system was extensively bench tested on fresh heart, liver and lung animal tissues using power levels of 30 - 60 W, RF energy delivery durations of 3 - 15 min and HS concentrations of 5% and 23.4%. Two swine were then treated at 60 W for 15 min per bronchus. Several bronchi were involved. For both animals and for all treatment sites, 20% HS was used. Animals were survived for six weeks. Results - Bench studies showed that 60 W, 7 - 15 min ablations can produce large ablation volumes, in excess of 3 - 4 cm diameter. In the chronic animal study, no clinically adverse events occurred. There was no evidence of hemorrhage. Animals vital signs, breathing patterns and their behavior were normal throughout the six-week period. Their appetite was normal and they gained weight according to expectations. The RF ablation created discrete volumes of thermal coagulative necrosis which were subsequently encapsulated ("walled off") by zones of organized fibrosis. The dimensions of coagulative necrotic sequestra met expectations, as at six weeks they exceeded volumes corresponding to 2 cm nodules, the size of tumors normally addressed in the peripheral lung by localized therapy. Conclusion - This therapy showed promise. Appropriate energy settings combined with suitable treatment locations safely produced large ablation volumes of uniform thermal coagulative necrosis. Further studies and optimization of treatment parameters can develop it into a mainstream therapy for treating early-stage lung tumors in humans.

Reduction in polyamine catabolism leads to spermine-mediated airway epithelial injury and induces asthma features.

BACKGROUND: Airway epithelial injury is a crucial component of acute and severe asthma pathogenesis and a promising target for treatment of refractory asthma. However, the underlying mechanism of epithelial injury remains poorly explored. Although high levels of polyamines, mainly spermine, have been found in asthma and comorbidity, their role in airway epithelial injury and the cause of their altered levels in asthma have not been explored. METHODS: We measured key polyamine metabolic enzymes in lung samples from normal and asthmatic subjects and in mice with OVA-induced allergic airway inflammation (AAI). Polyamine metabolism was modulated using pharmacologic/genetic modulators. Epithelial stress and apoptosis were measured by TSLP levels and TUNEL assay, respectively. RESULTS: We found loss of the polyamine catabolic enzymes spermidine/spermine-N (1)-acetyltransferase-1 (SAT1) and spermine oxidase (SMOX) predominantly in bronchial epithelial cells (BECs) of human asthmatic lung samples and mice with AAI. In naïve mice, SAT1 or SMOX knockdown led to airway hyper-responsiveness, remodeling, and BEC apoptosis. Conversely, in mice with AAI, overexpression of either SAT1 or SMOX alleviated asthmatic features and reduced TSLP levels and BEC apoptosis. Similarly, while pharmacological induction of SAT1 and SMOX using the polyamine analogue bis(ethyl)norspermine (BENSPM) alleviated asthmatic features with reduced TSLP levels and BEC apoptosis, pharmacological inhibition of these enzymes using BERENIL or MDL72527, respectively, worsened them. Spermine accumulation in lungs correlated with BEC apoptosis, and spermine treatment caused apoptosis of human BEAS-2B cells in vitro. CONCLUSIONS: Spermine induces BEC injury. Induction of polyamine catabolism may represent a novel therapeutic approach for asthma via reversing BEC stress.

Multicentric Cryptococcosis in a Congo African Grey Parrot ( Psittacus erithacus erithacus).

An approximately 10-year-old, female Congo African grey parrot ( Psittacus erithacus erithacus) developed progressive, unilateral exophthalmos and buphthalmos. Survey radiographs revealed a large, coelomic, soft tissue mass, which was confirmed on computed tomography scan. Aspirates of both the contents of the buphthalmic globe and coelomic mass were consistent with Cryptococcus species. Initial results were later confirmed with serum antigen latex agglutination and polymerase chain reaction testing, and the organism was then identified as Cryptococcus neoformans with DNA sequencing. During the course of 1 year, the bird was treated with combinations of oral terbinafine, fluconazole, and flucytosine, as well as intraocular amphotericin B. The coelomic mass dramatically decreased in size during the course of treatment, but the globe continued to enlarge. The bird died after exhibiting ataxia and seizures approximately 13 months after initial diagnosis, and necropsy confirmed colonization of the cerebrum and meninges with Cryptococcus. Cryptococcus remains a rare fungal disease of birds that is often refractory to treatment.

ISSR markers for gender identification and genetic diagnosis of Hippophae rhamnoides ssp. turkestanica growing at high altitudes in Ladakh region (Jammu and Kashmir).

Hippophae rhamnoides L. ssp. turkestanica (Elaeagnaceae) is a predominantly dioecious and wind-pollinated medicinal plant species. The mature fruits of the species possess antioxidative, anti-inflammatory, antimicrobial, anticancerous, and antistimulatory properties that are believed to improve the immune system. The identification of male and female plants in H. rhamnoides ssp. turkestanica is quite difficult until flowering which usually takes 3-4 years or more. A sex-linked marker can be helpful in establishing the orchards through identification of genders at an early stage of development. Therefore, we studied the genetic diversity of populations in Ladakh with the aim to identify a gender-specific marker using ISSR markers. Fifty-eight ISSR primers were used to characterize the genome of H. rhamnoides ssp. turkestanica, of which eight primers generated 12 sex-specific fragments specific to one or more populations. The ISSR primer (P-45) produced a fragment which faithfully segregates all the males from the female plants across all the three valleys surveyed. This male-specific locus was converted into a SCAR. Forward and reverse primers designed from this fragment amplified a 750-bp sequence in males only, thus specifying it as an informative male-specific sex-linked marker. This SCAR marker was further validated for its capability to differentiate gender on an additional collection of plants, representing three geographically isolated valleys (Nubra, Suru, and Indus) from Ladakh region of India. The results confirmed sex-linked specificity of the marker suggesting that this conserved sequence at the Y chromosome is well preserved through the populations in Ladakh region. At present, there are no reliable markers which can differentiate male from female plants across all the three valleys of Ladakh region at an early stage of plant development. It is therefore envisaged that the developed SCAR marker shall provide a reliable molecular tool for early identification of the sex in this commercial crop. The genetic diversity of populations as surveyed by ISSR primers revealed 85.71 % polymorphism at the population level. The dendrogram obtained divided the genotypes into three different clusters, and the distribution of male and female genotypes in all the clusters was random. The Nei's genetic similarity index was in the range of 0.63-0.96.

Study of efficacy and safety of modified adjuvant intraperitoneal chemotherapy regimen in carcinoma ovary.

OBJECTIVE: It has been demonstrated in few trials that intraperitoneal and intravenous (IP/IV) chemotherapy improves survival in advanced stage ovarian cancer (OC). However, in view of high treatment-related toxicities, various modifications in treatment schedules have been tried. In this study, response and tolerability of IP paclitaxel on day 8 with IV paclitaxel on day 1 and IV cisplatin day 2 in carcinoma ovary were evaluated. PATIENTS AND METHODS: In this prospective observational study, from March 2013 to December 2015, the efficacy and tolerability of adjuvant IP/IV chemotherapy in optimally cytoreduced Stage III epithelial OC (EOC) patients were assessed. RESULTS: Totally, sixty patients were enrolled. The median age of patients was 53 years (32-67 years). Out of a total of 360 IP cycles, 316 cycles (88%) were completed. Forty-five patients (76%) received all the 6 cycles by IP route. Eight out of those 45 patients had one or more adjustment including delay or dose reduction. After median follow-up of 22 months, eight patients (14%) had local or systemic recurrence. Median progression-free survival not reached yet. Catheter block was seen in five cases. Two cases had needle displacement and extravasations of drug around the port chamber. Six patients had Grade 3 abdominal pain and cramp. Grade 3/4 leukopenia was experienced by thirty patients (50%), but febrile neutropenia occurred in only 6 (10%) patients. Renal complication present in 4 (7%) patients. CONCLUSIONS: In Indian patients, adjuvant chemotherapy with day 8 I/P paclitaxel in optimally cytoreduced EOC is associated with comparable survival outcomes, less side effects and high treatment completion rate relative to literature published from Western countries.

Prevalence of autism spectrum disorders among children (1-10 years of age) - findings of a mid-term report from Northwest India.

BACKGROUND: India is the second most populous country of the world. A large portion of the population of this country is below 20 years of age but still there is a paucity of information about the prevalence and incidence of many developmental disorders. This study was planned to estimate the prevalence of autism spectrum disorders (ASDs) in the selected areas (tribal, rural, and urban) of a northern state of India, Himachal Pradesh. METHODS: A cross-sectional two-phase study was conducted covering all the children in the range of 1-10 years of age. Phase one included screening of all the children in the age group of 1-10 years, with the help of an indigenous assessment tool for autism. The sociodemographic profile of the participants was also recorded during phase one. Phase two involved the clinical evaluation of individuals who were suspected of autism on screening. RESULTS: The results show a prevalence rate of 0.9/1000. The highest prevalence rate was observed in the rural area. CONCLUSIONS: Socioeconomic status (SES) may be one of the fundamental indicators for ASDs in India.

Intersecting pentagons as surrogate for identifying the use of mini mental state examination in assessment of dementia in a largely illiterate population.

BACKGROUND AND RATIONALE: The mini-mental state evaluation (MMSE) is often used to identify patients with dementia. One component of the MMSE is the intersecting pentagon copying (IPC) test, which may be difficult to be used in an illiterate population. MATERIALS AND METHODS: A post hoc analysis on an elderly population (60 years and above) from Himachal Pradesh was carried out. The data of only 1,513 elderly individuals out of a total of 2,000 participants with a score of more than 26 (nondemented) out of a possible score of 30 on cognitive battery available were used. The scores on the IPC were evaluated and their association with some demographic variables was also assessed. RESULTS: Illiterate participants, female participants, those with greater age, and the rural/tribal population groups faced the most difficulty in drawing the intersecting pentagons and even greater difficulty in drawing them correctly. DISCUSSION: The IPC presents challenges for people who are illiterate and the scoring method needs to be addressed and changed particularly when the test is used in largely illiterate populations.

Facultative apomixis and development of fruit in a deciduous shrub with medicinal and nutritional uses.

Knowledge of reproductive biology of plants is crucial to understand their natural mode of propagation, which may aid in conservation and crop improvement. The reproductive details are also crucial for beginning the cultivation of a potential crop on a commercial scale. Fruits of sea buckthorn, Hippophae rhamnoides, are used in a variety of medicinal and nutritional products. So far, fruits are collected from the female plants in the wild. It is known that the species fruits profusely and also propagates by forming root suckers, but the details of sexual reproduction are not available. We investigated the mode of reproduction and development of fruits from natural populations of sea buckthorn. Megasporogenesis and megagametogenesis were studied through resin-embedded sectioning and ovule-clearing methods, and fruit development through histochemistry. The study of mitosis and male meiosis showed that the plants at the site were diploid (2n = 2x = 24). The embryo sac may develop either through the monosporic pathway and differentiates into 'Polygonum type' or aposporously into 'Panicum type'. The embryo may develop by sexual and adventitious pathways. Thus, sea buckthorn is a facultative apomict. The occurrence of diverse reproductive pathways assures the possibility of generation of novel genotypes through sexuality, while apomictic reproduction maintains adaptive genotypes and ensures reproduction in the absence of pollination. Anatomical details suggest that the fruit of sea buckthorn may be appropriately described as a pseudo-drupe.