A phase 3b study of venetoclax and azacitidine or decitabine in an outpatient setting in patients with acute myeloid leukemia.

Venetoclax, a highly selective BCL-2 inhibitor, combined with hypomethylating agents (HMAs) azacitidine or decitabine, is approved for the treatment of newly diagnosed acute myeloid leukemia (ND AML) in patients who are ineligible to receive intensive chemotherapy. Previous clinical studies initiated venetoclax plus HMA in an inpatient setting owing to concerns of tumor lysis syndrome (TLS). This study (NCT03941964) evaluated the efficacy and safety of venetoclax plus HMA in a United States community-based outpatient setting in patients with ND AML (N = 60) who were treatment naïve for AML, ineligible to receive intensive chemotherapy, had no evidence of spontaneous TLS at screening, and were deemed as appropriate candidates for outpatient initiation of venetoclax plus HMA by the investigator. Patients received venetoclax in combination with azacitidine (75 mg/m2) or decitabine (20 mg/m2) for up to 6 cycles during the study. With a median time on study of 18.3 weeks, the best response rate of composite complete remission was 66.7%, and the overall post-baseline red blood cell (RBC) and platelet transfusion independence rate was 55.0%, consistent with results of studies in which treatment was initiated in an inpatient setting. Key adverse events included nausea, anemia, thrombocytopenia, neutropenia, and white blood cell count decrease of any grade (≥50% of patients). The observed safety profile was generally consistent with that of venetoclax plus HMA observed in inpatient AML studies. With close monitoring, 2 cases of TLS were identified, appropriately managed, and the patients were able to continue study treatment. CLINICAL TRIALS REGISTRATION: This study is registered at ClinicalTrials.gov. The registration identification number is NCT03941964.

Radiation induced mutagenesis, physio-biochemical profiling and field evaluation of mutants in sugarcane cv. CoM 0265.

PURPOSE: Sugarcane is an important cash crop and is affected by soil salinity. CoM 0265, a moderately salt-tolerant variety grown in the Maharashtra region (India), has low sugar content. The present study was aimed to employ gamma ray induced in vitro mutagenesis with repeated and step-wise selection in sugarcane for the isolation and physio-biochemical profiling of the selected salt-tolerant mutants for improved agronomic performance and sugar content. MATERIALS AND METHODS: Embryogenic callus culture of CoM 0265 variety was subjected to different doses of gamma radiation (10, 20, 30, 40, 50, and 60 Gy) followed by selection on NaCl containing media (50, 100, 150, 200, and 250 mM NaCl). The regenerated plantlets were hardened and selected based on ground nursery field trial on normal soil and saline field trial, in augmented block design for the selected mutant clones. Different physio-biochemical changes and activity of antioxidant enzymes were analyzed in the salt selected in vitro cultures and field-grown mutant clones. RESULTS: Dose optimization showed 40 Gy as the LD50 for gamma radiation and 150 mM NaCl as the dose for in vitro selection experiments. The selected mutant clones showed higher tissue water content (TWC), chlorophyll, and lower sodium content indicative of tolerance to salt stress. Catalase and peroxidase enzyme activities in the top visible dewlap (TVD) of the putative mutant clones were significantly higher than the control. The average yield and sucrose percent of the selected mutant clones were significantly higher than control checks in the saline field trial. Mutant clones M8457 and M8721 exhibited improved yield and commercial cane sugar over the parent control check varieties under saline field conditions. Catalase activity was strongly associated with TWC (r = 0.34) and chlorophyll content (r = 0.41) while it was negatively correlated with sodium ion content (r = -0.38). Peroxidase activity in TVD also showed a significant positive correlation with chlorophyll content (r = 0.42) and a negative correlation with sodium ion content (r=-0.39). The improvement in yield and CCS (t/ha) was strongly associated with the lower sodium ion content of the mutant clones (r=-0.54 and -0.53, respectively). CONCLUSIONS: Gamma ray induced mutants were isolated for improved sucrose and high yield in sugarcane var. CoM 0265. The results suggest that gamma radiation induced mutations result in physiological and metabolomic alterations for better growth and adaptation under in vitro and field stress conditions in sugarcane. The improved mutants can be further useful for commercial cultivation in saline areas.

Automated Assessment of Thoracic-Abdominal Asynchrony in Patients with Morquio Syndrome.

Morquio syndrome is a rare disease caused by a disorder in the storage of mucopolysaccharides that affects multiple organs, including musculoskeletal, respiratory, cardiovascular, and digestive systems. Respiratory failure is one of the leading causes of mortality in Morquio patients; thus, respiratory function testing is vital to the management of the disease. An automated respiratory assessment methodology using the pneuRIP device and a machine-learning algorithm was developed. pneuRIP is a noninvasive approach that uses differences between thoracic and abdominal movements (thoracic-abdominal asynchrony) during respiration to assess respiratory status. The technique was evaluated on 17 patients with Morquio (9 females and 8 males) between the ages of 2 and 57 years. The results of the automated technique agreed with the clinical assessment in 16 out of the 17 patients. It was found that the inverse cumulative percentage representation of the time delay between the thorax and abdomen was the most critical variable for accurate evaluation. It was demonstrated that the technique could be successfully used on patients with Morquio who have difficulty breathing with 100% compliance. This technique is highly accurate, portable, noninvasive, and easy to administer, making it suitable for a variety of settings, such as outpatient clinics, at home, and emergency rooms.

Design, synthesis, in silico, and in vitro evaluation of 3-phenylpyrazole acetamide derivatives as antimycobacterial agents.

Mycobacterium tuberculosis (Mtb) is one of the most dangerous pathogens affecting immunocompetent and immunocompromised patients worldwide. Novel molecules, which are efficient and can reduce the duration of therapy against drug-resistant strains, are an urgent unmet need of the hour. In our current study, a series of new 2-(3-phenyl-1H-pyrazol-1-yl)acetamide and N'-benzylidene-2-(3-phenyl-1H-pyrazol-1-yl)acetohydrazide derivatives were designed, synthesized, and evaluated for their antimycobacterial potential. The biological evaluation revealed that 6b, 6m, 6l, 7a, and 7k exhibited selective and potent inhibitory activity against Mtb. Furthermore, compounds 6m and 7h were found to be nontoxic to Vero cells with CC50 of greater than 20 and 80 mg/ml, respectively, and exhibited promising selectivity indices (SI) of greater than 666 and 320, respectively. All derivatives exhibited excellent ADME (absorption, distribution, metabolism, and excretion) properties in silico. Also, all the derivatives were found compliant with Lipinski's rule of five, showing their druggability profile. Molecular docking insights of these derivatives have shown outstanding binding energies on the mycobacterial membrane protein large transporters. These results indicate that this scaffold may lead to a potential antimycobacterial drug candidate in the discovery of antitubercular agents.

Machine learning for automatic identification of thoracoabdominal asynchrony in children.

BACKGROUND: The current methods for assessment of thoracoabdominal asynchrony (TAA) require offline analysis on the part of physicians (respiratory inductance plethysmography (RIP)) or require experts for interpretation of the data (sleep apnea detection). METHODS: To assess synchrony between the thorax and abdomen, the movements of the two compartments during quiet breathing were measured using pneuRIP. Fifty-one recordings were obtained: 20 were used to train a machine-learning (ML) model with elastic-net regularization, and 31 were used to test the model's performance. Two feature sets were explored: (1) phase difference (ɸ) between the thoracic and abdominal signals and (2) inverse cumulative percentage (ICP), which is an alternate measure of data distribution. To compute accuracy of training, the model outcomes were compared with five experts' assessments. RESULTS: Accuracies of 61.3% and 90.3% were obtained using ɸ and ICP features, respectively. The inter-rater reliability (i.r.r.) of the assessments of experts was 0.402 and 0.684 when they used ɸ and ICP to identify TAA, respectively. CONCLUSIONS: With this pilot study, we show the efficacy of the ICP feature and ML in developing an accurate automated approach to identifying TAA that reduces time and effort for diagnosis. ICP also helped improve consensus among experts. IMPACT: Our article presents an automated approach to identifying thoracic abdominal asynchrony using machine learning and the pneuRIP device. It also shows how a modified statistical measure of cumulative frequency can be used to visualize the progression of the pulmonary functionality along time. The pulmonary testing method we developed gives patients and doctors a noninvasive and easy to administer and diagnose approach. It can be administered remotely, and alerts can be transmitted to the physician. Further, the test can also be used to monitor and assess pulmonary function continuously for prolonged periods, if needed.

Metabolic variations in normal and fibrotic human laryngotracheal-derived fibroblasts: A Warburg-like effect.

OBJECTIVES/HYPOTHESIS: Laryngotracheal stenosis (LTS) is a chronic fibrotic disease characterized by fibroblast proliferation, collagen deposition, and matrix remodeling in the lamina propria of the larynx and/or trachea. Current medical therapies are limited by a poor understanding of the effector cell's (fibroblasts) cellular biology and metabolism. The purpose of this study was to compare cellular proliferation, function, and metabolism between normal and LTS-derived fibroblasts in vitro. We hypothesize that LTS-derived fibroblasts will demonstrate aberrant behavior with faster proliferation, increased collagen production, and altered metabolic allocation compared with normal fibroblasts. STUDY DESIGN: In vitro comparative analysis. METHODS: Human biopsies of normal and iatrogenic LTS tissue (n = 7) were obtained, and fibroblasts were isolated and cultured in vitro. Cellular proliferation, cellular histology, gene expression, and metabolic analyses were performed. Statistical analyses comparing normal and scar-derived fibroblasts were performed. RESULTS: LTS fibroblast proliferation rate, cellular surface area, and collagen-1 expression were increased compared to normal fibroblasts. Cellular metabolic analysis of LTS-derived fibroblasts demonstrated reduced oxidative phosphorylation and increased glycolysis/oxidative phosphorylation ratio compared with normal fibroblasts. CONCLUSIONS: Human iatrogenic LTS-derived fibroblasts demonstrated aberrant behavior when compared with normal fibroblasts. A Warburg-like effect was revealed, suggesting human iatrogenic LTS fibroblasts drive their proliferation with aerobic glycolysis. The distinct metabolism suggests metabolic inhibitors could reduce fibroblast hyperplasia and hypertrophy in LTS and fibrosis in general. LEVEL OF EVIDENCE: NA Laryngoscope, 127:E107-E113, 2017.

Differential expression of human placental neurotrophic factors in preterm and term deliveries.

Neurotrophic factors such as brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are involved in development of the placenta and fetal brain. A series of human and animal studies in our department have shown that micronutrients (folic acid, vitamin B12) and omega 3 fatty acids like DHA are all interlinked in the one carbon cycle. Any alterations in one carbon components will lead to changes in methylation patterns that further affect the gene expression at critical periods of development resulting in complications during pregnancy. This may further contribute to risk for neurodevelopmental disorders in children born preterm. Therefore this study for the first time examines the mRNA levels from preterm and term placentae. A total number of 38 women delivering preterm (<37 weeks gestation) and 37 women delivering at term (=>37 weeks gestation) were recruited. The mRNA levels of BDNF and NGF were analyzed by real time quantitative polymerase chain reaction. Our results indicate that BDNF and NGF mRNA levels were lower in preterm group as compared to term group. There was a positive association of placental BDNF and NGF mRNA levels with cord plasma BDNF and NGF levels. The differential expression of BDNF and NGF gene in preterm placentae may also alter the vascular development in preterm deliveries. Our data suggests that the reduced mRNA levels of BDNF and NGF may possibly be a result of altered epigenetic mechanisms and may have an implication for altered fetal programming in children born preterm.

A selective and sensitive UPLC-MS/MS approach for trace level quantification of four potential genotoxic impurities in zolmitriptan drug substance.

The pivotal task of pharmaceutical industry is to separate and quantify the potential genotoxic impurities (PGIs) rising from the process of drug production. For trace level quantification of these PGIs we need to develop sensitive and selective analytical methods. APP, NPA, NPP and MNA have been highlighted as PGIs in zolmitriptan. A sensitive and selective UPLC-MS/MS method has developed for identification and quantification of four PGIs viz. APP, NPA, NPP and MNA in zolmitriptan. The method utilizes Hypersil BDS C8 column (50 mm × 4.6 mm, 3.0 µm) with electrospray ionization in selected ion recording (SIR) mode for quantitation of four PGIs. The method was validated as per International Conference on Harmonization (ICH) guidelines and is able to quantitate APP at 0.1 ppm and NPA, NPP and MNA at 0.15 ppm with respect to 5.0mg/mL of zolmitriptan. The proposed method is specific, linear, accurate and precise. The method is linear in the range of 0.1-2.0 ppm for APP and 0.15-2.0 ppm for NPA, NPP and MNA, which matches the range of LOQ-200% of estimated permitted level (1.0 ppm). The correlation coefficient obtained was >0.999 in each case. The impurities were not present in the studied three pure and formulation batches of zolmitriptan. The accuracy of the method was ranged between 98.1 and 102.8% for four PGIs. This method is a good quality control tool for quantitation of four APP, NPA, NPP and MNA PGIs at very low levels in zolmitriptan.

Decolorization and detoxification of sulfonated azo dye C.I. Remazol Red and textile effluent by isolated Lysinibacillus sp. RGS.

A novel bacterium was isolated from the soil of Ichalkaranji textile industrial area. Through 16S rRNA sequence matching and morphological observation it was identified as Lysinibacillus sp. RGS. This strain has ability to decolorize various industrial dyes among which, it showed complete decolorization and degradation of toxic sulfonated azo dye C.I. Remazol Red (at 30°C, pH 7.0, under static condition) with higher chemical oxygen demand (COD) reduction (92%) within 6 h of incubation. Various parameters like agitation, pH, temperature and initial dye concentrations were optimized to develop faster decolorization process. The supplementation of cheap co-substrates (e.g., extracts of agricultural wastes) could enhance the decolorization performance of Lysinibacillus sp. RGS. Induction in oxidoreductive enzymes presumably indicates involvement of these enzymes in the decolorization/degradation process. Analytical studies of the extracted metabolites confirmed the significant degradation of Remazol Red into various metabolites. The phytotoxicity assay (with respect to plants Phaseolus mungo and Sorghum vulgare) revealed that the degradation of Remazol Red produced nontoxic metabolites. Finally Lysinibacillus sp. RGS was applied to decolorize mixture of dyes and actual industrial effluent showing 87% and 72% decolorization (in terms of decrease in ADMI value) with 69% and 62% COD reduction within 48 h and 96 h, respectively. The foregoing result increases the applicability of the strain for the treatment of industrial wastewaters containing dye pollutants.

Systematic Approach for Trace Level Quantification of 2-N-butyl-4-spirocyclopentane-2-imidazole-5-one Genotoxic Impurity in Irbesartan Using LC-MS/MS.

2-N-butyl-4-spirocyclopentane-2-imidazoline-5-one has been highlighted as a potential genotoxic impurity in irbesartan. A sensitive LC-MS/MS method was developed and validated for the determination of 2-N-butyl-4-spirocyclopentane-2-imidazoline-5-one in irbesartan. Good separation between 2-N-butyl-4-spirocyclopentane-2-imidazoline-5-one and irbesartan was achieved with Symmetry C18 (100×4.6 mm, 3.5 µm) column using 65:35 v/v mixture of 0.1% formic acid and acetonitrile as mobile phase with a flow rate of 0.7 ml/min. The proposed method was specific, linear, accurate, and precise. The calibration curve shows good linearity over the concentration range of 0.1-2.0 µg/ml, which matches the range of limit of quantitation-20×limit of quantitation of estimated permitted level (1.0 µg/ml) of 2-N-butyl-4-spirocyclopentane-2-imidazoline-5-one. The method was validated as per International Conference on Harmonization guidelines and was able to quantitate 2-N-butyl-4-spirocyclopentane-2-imidazoline-5-one impurity at 1.0 µg/ml with respect to 2 mg/ml of irbesartan. 2-N-butyl-4-spirocyclopentane-2-imidazoline-5-one was not present in the three studied pure and formulation batches of irbesartan and the developed method was a good quality control tool for quantitation of 2-N-butyl-4-spirocyclopentane-2-imidazole-5-one at very low levels in irbesartan.

Method development and validation study for quantitative determination of 2-chloromethyl-3,4-dimethoxy pyridine hydrochloride a genotoxic impurity in pantoprazole active pharmaceutical ingredient (API) by LC/MS/MS.

A sensitive and selective liquid chromatographic-tandem mass spectrometric (LC/MS/MS) method was developed and validated for the trace analysis (>1 ppm level) of 2-chloromethyl-3,4-dimethoxy pyridine hydrochloride a genotoxic impurity in pantoprazole sodium drug substances. LC/MS/MS analysis of 2-chloromethyl-3,4-dimethoxy pyridine hydrochloride was done on Hypersil BDS C18 (50 mm × 4.6 mm) 3 µm column and 10 mM ammonium acetate in 1000 mL of water was used as buffer. The mobile phase used was in the ratio of buffer-acetonitrile (79:21, v/v). The flow rate was 1.0 mL/min and elution was monitored at 210 nm. The method was validated as per International Conference on Harmonization (ICH) guidelines. LC/MS/MS is able to quantitate up to 0.3 ppm of 2-chloromethyl-3,4-dimethoxy pyridine hydrochloride.

Provocative dietary factors in geriatric hypertension: A surveillance study.

Hypertension is the most common psychosomatic disorder affecting 972 million people worldwide being more prevalent in old age. The present survey of hypertensive patients fulfilling the standard diagnostic criteria of WHO/ISH (2004) is carried out in geriatric age group from the Saurashtra region of Gujarat in India to observe the dietary pattern and provocative factors. Total 120 patients of 50 to 80 years of age having systolic blood pressure >140 mm Hg and ≤180 mm Hg and diastolic blood pressure >90 mm Hg and ≤110 mm Hg irrespective of gender and religion were selected for the present study. They were interviewed for list of provocative factors enlisted in Ayurveda. As observed, the study supported the facts described in Ayurveda that dietary etiological factors, such as excess intake of Lavana (salty), Amla (sour), Katu (pungent), Tikshna, Ushna (hot), Vidahi (producing burning sensation), Viruddha (incompatible), Snigdha (unctuous), Abhishyandi (leading to obstruction), Madhura (sweet), Guru (heavy to digest) dietary articles, Ajirnashana (taking diet before complete digestion of previous meal), Adhyashana (repeated eating at short intervals), will vitiate Rakta dhatu as well as Pitta dosha in the body leading to disorders like hypertension. Hypertension in old age is found to be a disease of Vata-Pitta dominant vitiation with the involvement of Rasa, Rakta, Meda as main Dushya (vitiated factors) and dietary factors can contribute to worsening of the disease. The etiological factors having role in the pathogenesis can also be applied for preventive guidelines for the management of hypertension.

Reduced levels of placental long chain polyunsaturated fatty acids in preterm deliveries.

Reports suggest that the placenta in preterm birth may provide clues to predicting the risk of individuals developing chronic diseases in later life. Placental delivery of long chain polyunsaturated fatty acids (LCPUFA) (constituents of the cell membrane and precursors of prostaglandins) is essential for the optimal development of the central nervous system of the fetus. The present study examines the levels of LCPUFA and their association with placental weight and birth outcome in 58 women delivering preterm and 44 women delivering at term. Docosahexaenoic acid (DHA) and arachidonic acid (ARA) levels were lower (p<0.01) in women delivering preterm. There was a positive association of placental DHA with placental weight (p=0.036) and nervonic acid with head circumference (p=0.040) in the preterm group. Altered placental LCPUFA status exists in Indian mothers delivering preterm, which may influence the birth outcome.

Development and characterization of new cell line BPH22 from midgut epithelial cells of Poekilocerus pictus (Fabricius, 1775).

Poekilocerus pictus is a painted grasshopper, which feeds on Calotropis sp. containing the cardiac glycosides. A new cell line BPH22 is developed from midgut of P. pictus to study its unique physiology and biochemistry. Initially, the Graces insect medium is used with 10% (v/v) fetal bovine serum. After four passages, the serum quantity was reduced up to 0%.The lag phase in growth curve was 5 d and log phase is up to 10-11 d. The addition of Calotropis extract in Graces medium enhanced the growth of cells. The Calotropis extract with Graces medium altered the morphology of cells of BPH22. The amplification and sequencing of 16S rRNA gene confirmed the origin and purity of the BPH22.

Effect of particle size variation of Ag nanoparticles in Polyaniline composite on humidity sensing.

The results of synthesis of Ag-Polyaniline nanocomposite along with an investigation of optical fiber based humidity sensor using evanescent wave absorption spectroscopy are discussed. The sensor was fabricated using Ag-Polyaniline nanocomposite deposited on an optical fiber clad and tested in the range of 5-95% relative humidity (RH). Optimization of clad length (2-8mm) was done and then particle size (15-30 nm) variation of silver nanoparticles in Polyaniline composite was studied for better performance of sensor. The effect of particle size on sensing humidity was investigated. The reduction of particle size, leads to a dramatic improvement in sensitivity and speed of response. The optimized clad length of 6mm exhibits the better results for 15 nm particle size of Ag nanoparticles dispersed in Polyaniline. The sensor response is fully reversible having almost 1% of standard deviation. Response time of the sensor is 30s with a slow recovery of 90 s.

Long chain polyunsaturated fatty acids in mothers and term babies.

AIM: To establish the levels of docosahexaenoic acid (DHA) and arachidonic acid (AA) in both plasma and erythrocytes of maternal and cord blood as well as in breast milk of mothers delivering babies at term. METHODS: A total of 148 mothers delivering babies at term were recruited from Bharati Medical Hospital, Pune, India. RESULTS: Levels of DHA and AA in both plasma and erythrocyte were higher in cord blood compared to levels in maternal blood (P<0.001). Maternal plasma and erythrocyte DHA levels had a positive association with the respective levels in cord blood (P<0.001). However, such an association was not seen for AA levels. Maternal plasma omega 3 and omega 6 fatty acids were positively associated with the respective milk fatty acids (P<0.01). CONCLUSIONS: Our results indicate that milk long-chain polyunsaturated fatty acids (LCPUFA) status reflects the concentrations of maternal LCPUFA in women delivering babies at term. Improving the maternal LCPUFA status throughout pregnancy and lactation may improve the milk LCPUFA status and ultimately benefit the infant.

Electrical and humidity characterization of m-NA doped Au/PVA nanocomposites.

The Meta-Nitroaniline (m-NA) doped (by varying weight percentage (wt. %)) gold/polyvinyl alcohol (Au/PVA) nanocomposites were synthesized using gold salt and hydrazine hydrate (HH) by in situ process. The composite was coated on ceramic rods having two end electrodes by drop casting method for studying their electrical behavior at different relative humidity (RH) levels, ranging from 4 to 95% RH at room temperature. The optimized wt. % was used to prepare coatings of various thicknesses (20-40 microm) of the films. As the humidity decreases, the resistance increases. The low humidity sensing characteristic can be tailored by varying wt. % of m-NA and thicknesses of the nanocomposite films. The resistive-humidity sensor shows two regions of sensitivity having highest sensitivity for lower RH. The sensor response and recovery time is about 6-10s and 52 s respectively. The dynamic range of variation of the resistance allows a promising use of the films as a humidity sensor. The material was characterized by X-ray diffraction (XRD) and impedance spectroscopy at 60% RH.

Evaluation of co-polyaniline nanocomposite thin films as humidity sensor.

Spin coated films of Co-Polyaniline nanocomposite are evaluated for their transmission properties using He-Ne laser for humidity sensing. The thickness (17-29 microm) of the films is varied by multiple deposition of Co-Polyaniline nanocomposite on a glass substrate. The samples exhibit typically two to three regions in their sensitivity curve when tested in the relative humidity (RH) range of 20-95%. The sensitivity ranges from 0.1 mV/%RH to 12.26 mV/%RH for lower to higher thickness. The sensors show quick response of 8s (20-95%RH), and a recovery time of 1 min (95-20%RH) with good repeatability, reproducibility and low hysteresis effect. The sensitivity of the sensor increases with humidity and thickness. Material characterization is done by X-ray diffraction (XRD), scanning electron micrograph (SEM) and Fourier transform infra-red spectroscopy (FTIR).

STR data for the Amp FlSTR Profiler Plus loci among 27 populations of different social hierarchy from southern part of Andhra Pradesh, India.

Allele frequency for the 9 STR loci (D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820) were estimated from a total of 1096 individuals belonging to 27 endogamous populations from the state of Andhra Pradesh, India, covering the entire gamut of socio-economic variation of the linguistic region. These loci are found to be highly polymorphic within the populations with high levels of average heterozygosity (>0.80). However, the allele frequency distributions are fairly uniform across the populations in case of these loci suggesting relatively greater homogeneity among the populations. Regrouping populations into five broad socio-economic categories further reiterated the homogenous pattern of genetic diversity.

Microsatellite diversity in Andhra Pradesh, India: genetic stratification versus social stratification.

DNA samples of 948 individuals belonging to 27 populations from southern Andhra Pradesh were analyzed for nine AmpFlSTR Profiler Plus loci. The nature and extent of genomic diversity within and between these populations have been examined with reference to socioeconomic and geographic affiliations. The results suggest that the average heterozygosity is uniformly high in these populations (> 0.80) and that the patterns of allele distributions are similar across the populations. The value of the coefficient of gene differentiation and the AMOVA and structure analysis results suggest that these populations are highly homogeneous. The neighbor-joining tree constructed using either D(A) or F(ST) distances suggests no intelligible pattern of population clusters based on ethnohistoric or geographic affiliations. All these observations suggest either a common recent origin of these populations or extensive gene flow across the populations that erased the original genetic differences. Given strict endogamy, the latter explanation can hold only if there has been unauthorized or unrecognized gene flow transecting the social boundaries. Nevertheless, the regression plot of average heterozygosity versus distance from the centroid (Rii), based on Harpending and Ward's (1982) model, and the genetic distances computed between different hierarchical groups within Andhra Pradesh tend to support this conjecture. Overall, the results suggest lack of a significant degree of genetic stratification that is consistent with social stratification in Andhra Pradesh. Furthermore, the neighbor-joining tree based on comparative data from other Indian and continental populations brings out a single and compact cluster of all the Andhra populations that is clearly separated from the rest.