Childhood adversities characterize the heterogeneity in the brain pattern of individuals during neurodevelopment.

BACKGROUND: Several factors shape the neurodevelopmental trajectory. A key area of focus in neurodevelopmental research is to estimate the factors that have maximal influence on the brain and can tip the balance from typical to atypical development. METHODS: Utilizing a dissimilarity maximization algorithm on the dynamic mode decomposition (DMD) of the resting state functional MRI data, we classified subjects from the cVEDA neurodevelopmental cohort (n = 987, aged 6-23 years) into homogeneously patterned DMD (representing typical development in 809 subjects) and heterogeneously patterned DMD (indicative of atypical development in 178 subjects). RESULTS: Significant DMD differences were primarily identified in the default mode network (DMN) regions across these groups (p < 0.05, Bonferroni corrected). While the groups were comparable in cognitive performance, the atypical group had more frequent exposure to adversities and faced higher abuses (p < 0.05, Bonferroni corrected). Upon evaluating brain-behavior correlations, we found that correlation patterns between adversity and DMN dynamic modes exhibited age-dependent variations for atypical subjects, hinting at differential utilization of the DMN due to chronic adversities. CONCLUSION: Adversities (particularly abuse) maximally influence the DMN during neurodevelopment and lead to the failure in the development of a coherent DMN system. While DMN's integrity is preserved in typical development, the age-dependent variability in atypically developing individuals is contrasting. The flexibility of DMN might be a compensatory mechanism to protect an individual in an abusive environment. However, such adaptability might deprive the neural system of the faculties of normal functioning and may incur long-term effects on the psyche.

Risk clustering and psychopathology from a multi-center cohort of Indian children, adolescents, and young adults.

Developmental adversities early in life are associated with later psychopathology. Clustering may be a useful approach to group multiple diverse risks together and study their relation with psychopathology. To generate risk clusters of children, adolescents, and young adults, based on adverse environmental exposure and developmental characteristics, and to examine the association of risk clusters with manifest psychopathology. Participants (n = 8300) between 6 and 23 years were recruited from seven sites in India. We administered questionnaires to elicit history of previous exposure to adverse childhood environments, family history of psychiatric disorders in first-degree relatives, and a range of antenatal and postnatal adversities. We used these variables to generate risk clusters. Mini-International Neuropsychiatric Interview-5 was administered to evaluate manifest psychopathology. Two-step cluster analysis revealed two clusters designated as high-risk cluster (HRC) and low-risk cluster (LRC), comprising 4197 (50.5%) and 4103 (49.5%) participants, respectively. HRC had higher frequencies of family history of mental illness, antenatal and neonatal risk factors, developmental delays, history of migration, and exposure to adverse childhood experiences than LRC. There were significantly higher risks of any psychiatric disorder [Relative Risk (RR) = 2.0, 95% CI 1.8-2.3], externalizing (RR = 4.8, 95% CI 3.6-6.4) and internalizing disorders (RR = 2.6, 95% CI 2.2-2.9), and suicidality (2.3, 95% CI 1.8-2.8) in HRC. Social-environmental and developmental factors could classify Indian children, adolescents and young adults into homogeneous clusters at high or low risk of psychopathology. These biopsychosocial determinants of mental health may have practice, policy and research implications for people in low- and middle-income countries.

Modulation of the 5-Lipoxygenase Pathway by Chalcogen-Containing Inhibitors of Leukotriene A4 Hydrolase.

The 5-lipoxygenase (5-LOX) pathway gives rise to bioactive inflammatory lipid mediators, such as leukotrienes (LTs). 5-LOX carries out the oxygenation of arachidonic acid to the 5-hydroperoxy derivative and then to the leukotriene A4 epoxide which is converted to a chemotactic leukotriene B4 (LTB4) by leukotriene A4 hydrolase (LTA4H). In addition, LTA4H possesses aminopeptidase activity to cleave the N-terminal proline of a pro-inflammatory tripeptide, prolyl-glycyl-proline (PGP). Based on the structural characteristics of LTA4H, it is possible to selectively inhibit the epoxide hydrolase activity while sparing the inactivating, peptidolytic, cleavage of PGP. In the current study, chalcogen-containing compounds, 4-(4-benzylphenyl) thiazol-2-amine (ARM1) and its selenazole (TTSe) and oxazole (TTO) derivatives were characterized regarding their inhibitory and binding properties. All three compounds selectively inhibit the epoxide hydrolase activity of LTA4H at low micromolar concentrations, while sparing the aminopeptidase activity. These inhibitors also block the 5-LOX activity in leukocytes and have distinct inhibition constants with recombinant 5-LOX. Furthermore, high-resolution structures of LTA4H with inhibitors were determined and potential binding sites to 5-LOX were proposed. In conclusion, we present chalcogen-containing inhibitors which differentially target essential steps in the biosynthetic route for LTB4 and can potentially be used as modulators of inflammatory response by the 5-LOX pathway.

Biosynthesis of prostaglandin 15dPGJ2 -glutathione and 15dPGJ2-cysteine conjugates in macrophages and mast cells via MGST3.

Inhibition of microsomal prostaglandin E synthase-1 (mPGES-1) results in decreased production of proinflammatory PGE2 and can lead to shunting of PGH2 into the prostaglandin D2 (PGD2)/15-deoxy-Δ12,14-prostaglandin J2 (15dPGJ2) pathway. 15dPGJ2 forms Michael adducts with thiol-containing biomolecules such as GSH or cysteine residues on target proteins and is thought to promote resolution of inflammation. We aimed to elucidate the biosynthesis and metabolism of 15dPGJ2 via conjugation with GSH, to form 15dPGJ2-glutathione (15dPGJ2-GS) and 15dPGJ2-cysteine (15dPGJ2-Cys) conjugates and to characterize the effects of mPGES-1 inhibition on the PGD2/15dPGJ2 pathway in mouse and human immune cells. Our results demonstrate the formation of PGD2, 15dPGJ2, 15dPGJ2-GS, and 15dPGJ2-Cys in RAW264.7 cells after lipopolysaccharide stimulation. Moreover, 15dPGJ2-Cys was found in lipopolysaccharide-activated primary murine macrophages as well as in human mast cells following stimulation of the IgE-receptor. Our results also suggest that the microsomal glutathione S-transferase 3 is essential for the formation of 15dPGJ2 conjugates. In contrast to inhibition of cyclooxygenase, which leads to blockage of the PGD2/15dPGJ2 pathway, we found that inhibition of mPGES-1 preserves PGD2 and its metabolites. Collectively, this study highlights the formation of 15dPGJ2-GS and 15dPGJ2-Cys in mouse and human immune cells, the involvement of microsomal glutathione S-transferase 3 in their biosynthesis, and their unchanged formation following inhibition of mPGES-1. The results encourage further research on their roles as bioactive lipid mediators.

Replication competence of canine distemper virus in cell lines expressing signaling lymphocyte activation molecule (SLAM) of goat, sheep and dog origin.

Cellular receptors play an important role in entry and cell to cell spread of morbillivirus infections. The cells expressing SLAM and Nectin-4 have been used for successful and efficient isolation of canine distemper virus (CDV) in high titre. There are several methods for generation of cells expressing receptor molecules. Here, we have used a comparatively cheaper and easily available method, pcDNA 3.1 (+) for engineering Vero cells to express SLAM gene of goat, sheep and dog origin (Vero/Goat/SLAM (VGS), Vero/Sheep/SLAM (VSS) and Vero/Dog/SLAM (VDS), respectively). The generated cell lines were then compared to test their efficacy to support CDV replication. CDV could be grown in high titre in the cells expressing SLAM and a difference of log two could be recorded in virus titre between VDS and native Vero cells. Also, CDV could be grown in a higher titre in VDS as compared to VGS and VSS. The finding of this study supports the preferential use of SLAM expressing cells over the native Vero cells by CDV. Further, the higher titre of CDV in cells expressing dog-SLAM as compared to the cells expressing SLAM of non-CDV hosts (i.e. goat and sheep) points towards the preferential use of dog SLAM by the CDV and may be a plausible reason for differential susceptibility of small ruminants and Canines to CDV.

Synthesis of Green/Blue Light Emitting Quinolines by Aza-D-A Reaction Using InCl3 Catalyst.

An efficient InCl3-catalyzed sequential reaction of aromatic amines, aromatic aldehydes and functionalized alkynes leading to the formation of new quinoline derivatives exhibiting significant fluorescence activities is described. The photophysical investigations of quinolines were carried out by absorption and photoluminescence measurements. One particular compound 4 h having maximum intensity, emitting green colour (Φ = 0.78) with average life time of 6.20 ns was the best amongst the tested compounds. The presence of the amino group at the 4-aryl substituent of the quinoline backbone played an important role in executing the Povarov cyclization successfully and enhancing the flourescence properties of the newly synthesized quinolines.

Structural and DNA binding properties of mycobacterial integration host factor mIHF.

In bacteria, nucleoid associated proteins (NAPs) take part in active chromosome organization by supercoil management, three-dimensional DNA looping and direct transcriptional control. Mycobacterial integration host factor (mIHF, rv1388) is a NAP restricted to Actinobacteria and essential for survival of the human pathogen Mycobacterium tuberculosis. We show in vitro that DNA binding by mIHF strongly stabilizes the protein and increases its melting temperature. The structure obtained by Nuclear Magnetic Resonance (NMR) spectroscopy characterizes mIHF as a globular protein with a protruding alpha helix and a disordered N-terminus, similar to Streptomyces coelicolor IHF (sIHF). NMR revealed no residues of high flexibility, suggesting that mIHF is a rigid protein overall that does not undergo structural rearrangements. We show that mIHF only binds to double stranded DNA in solution, through two DNA binding sites (DBSs) similar to those identified in the X-ray structure of sIHF. According to Atomic Force Microscopy, mIHF is able to introduce left-handed loops of ca. 100 nm size (~300 bp) in supercoiled cosmids, thereby unwinding and relaxing the DNA.

Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA): A developmental cohort study protocol.

BACKGROUND: Low and middle-income countries like India with a large youth population experience a different environment from that of high-income countries. The Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA), based in India, aims to examine environmental influences on genomic variations, neurodevelopmental trajectories and vulnerability to psychopathology, with a focus on externalizing disorders. METHODS: cVEDA is a longitudinal cohort study, with planned missingness design for yearly follow-up. Participants have been recruited from multi-site tertiary care mental health settings, local communities, schools and colleges. 10,000 individuals between 6 and 23 years of age, of all genders, representing five geographically, ethnically, and socio-culturally distinct regions in India, and exposures to variations in early life adversity (psychosocial, nutritional, toxic exposures, slum-habitats, socio-political conflicts, urban/rural living, mental illness in the family) have been assessed using age-appropriate instruments to capture socio-demographic information, temperament, environmental exposures, parenting, psychiatric morbidity, and neuropsychological functioning. Blood/saliva and urine samples have been collected for genetic, epigenetic and toxicological (heavy metals, volatile organic compounds) studies. Structural (T1, T2, DTI) and functional (resting state fMRI) MRI brain scans have been performed on approximately 15% of the individuals. All data and biological samples are maintained in a databank and biobank, respectively. DISCUSSION: The cVEDA has established the largest neurodevelopmental database in India, comparable to global datasets, with detailed environmental characterization. This should permit identification of environmental and genetic vulnerabilities to psychopathology within a developmental framework. Neuroimaging and neuropsychological data from this study are already yielding insights on brain growth and maturation patterns.

Elucidation of electrocoagulation mechanism in the removal of Blue SI dye from aqueous solution using Al-Al, Cu-Cu electrodes - A comparative study.

This work presents the research on the treatment of an anthraquinone derivatives of disperse dye Blue SI from aqueous solution using aluminium for the optimization of operational parameters like pH, current density, addition of electrolyte, contact time for the color removal efficiency (CRE) and the results are compared with the performance of copper electrodes in electrocoagulation (EC). The parameters for maximum CRE was found with Al at current density 40 Am-2, time 10 min at pH 7, and for Cu at 60 Am-2 15 min, at pH 6 were optimized. The characterization of the treated water using HPLC, MS studies revealed intermediate compounds. From the XPS analysis of the sludge obtained, the mechanism of EC was deduced. Treated aqueous solution was studied for its phytotoxicity with Vigna radiata and ecotoxicity studies were conducted on Artemia salina to study the toxicity effect of the intermediatory products in the treated dye solution. Blue SI dye aqueous solution treated with aluminium electrodes shows no or lesser toxicity in plants as well as in ecotoxic study compared with copper electrodes.

Structural and Functional Characterization of NadR from Lactococcus lactis.

NadR is a bifunctional enzyme that converts nicotinamide riboside (NR) into nicotinamide mononucleotide (NMN), which is then converted into nicotinamide adenine dinucleotide (NAD). Although a crystal structure of the enzyme from the Gram-negative bacterium Haemophilus influenzae is known, structural understanding of its catalytic mechanism remains unclear. Here, we purified the NadR enzyme from Lactococcus lactis and established an assay to determine the combined activity of this bifunctional enzyme. The conversion of NR into NAD showed hyperbolic dependence on the NR concentration, but sigmoidal dependence on the ATP concentration. The apparent cooperativity for ATP may be explained because both reactions catalyzed by the bifunctional enzyme (phosphorylation of NR and adenylation of NMN) require ATP. The conversion of NMN into NAD followed simple Michaelis-Menten kinetics for NMN, but again with the sigmoidal dependence on the ATP concentration. In this case, the apparent cooperativity is unexpected since only a single ATP is used in the NMN adenylyltransferase catalyzed reaction. To determine the possible structural determinants of such cooperativity, we solved the crystal structure of NadR from L. lactis (NadRLl). Co-crystallization with NAD, NR, NMN, ATP, and AMP-PNP revealed a 'sink' for adenine nucleotides in a location between two domains. This sink could be a regulatory site, or it may facilitate the channeling of substrates between the two domains.

Characterization of isolates of Bordetella bronchiseptica from horses.

Bordetella bronchiseptica is a well-known Gram-negative bacterial pathogen causing a plethora of diseases in different animals. Although its infection has been reported from pigs and dogs in India, no report of B. bronchiseptica from horses is described. We report for the first time, isolation, identification and characterization of strains of B. bronchiseptica from respiratory infection in horses from different states in India. The antimicrobial susceptibility testing showed resistance to penicillins, ceftazidime, and chloramphanicol. The virulence capability of the strains was confirmed by sequencing genes such as adenylate cyclase toxin (cyaA), bordetella virulence gene (bvgA) and by PCR detection of flagellin gene (fla). We demonstrate the involvement of B. bronchiseptica strains in respiratory tract infection in horses in India.

A new class of organogelators based on triphenylmethyl derivatives of primary alcohols: hydrophobic interactions alone can mediate gelation.

In the present work, we have explored the use of the triphenylmethyl group, a commonly used protecting group for primary alcohols as a gelling structural component in the design of molecular gelators. We synthesized a small library of triphenylmethyl derivatives of simple primary alcohols and studied their gelation properties in different solvents. Gelation efficiency for some of the derivatives was moderate to excellent with a minimum gelation concentration ranging between 0.5-4.0% w/v and a gel-sol transition temperature range of 31-75 °C. 1,8-Bis(trityloxy)octane, the ditrityl derivative of 1,8-octanediol was the most efficient organogelator. Detailed characterizations of the gel were carried out using scanning electron microscopy, FTIR spectroscopy, rheology and powder XRD techniques. This gel also showed a good absorption profile for a water soluble dye. Given the non-polar nature of this molecule, gel formation is likely to be mediated by hydrophobic interactions between the triphenylmethyl moieties and alkyl chains. Possible self-assembled packing arrangements in the gel state for 1,8-bis(trityloxy)octane and (hexadecyloxymethanetriyl)tribenzene are presented. Results from this study strongly indicate that triphenylmethyl group is a promising gelling structural unit which may be further exploited in the design of small molecule based gelators.

Antioxidant and antimicrobial properties of grape and papaya seed extracts and their application on the preservation of Indian mackerel (Rastrelliger kanagurta) during ice storage.

Antioxidant properties of grape (GSE) and papaya seed extracts (PSE) were tested in vitro at varied concentrations and growth inhibition were seen against gram positive and gram negative bacteria by disc diffusion method. The results revealed that GSE contain four times higher phenolic and six folds higher flavonoid content than PSE. The antioxidant properties of GSE and PSE showed dose dependent activities and were comparatively much higher in GSE. Linoleic acid model of GSE and PSE displayed 67.67 and 46.43 % of inhibition respectively at 500 mg/L. The effect of dip treatment by GSE and PSE at a concentration of 500 and 1000 mg/L respectively on the quality changes of Indian mackerel (Rastrelliger kanagurta) in iced condition were assessed using chemical, microbiological and sensory parameters along with chilled whole control (CWC). The inhibition of primary and secondary lipid oxidation products by GSE at 500 mg/L was comparable to BHT at 200 mg/L. GSE exhibited higher antimicrobial activity on gram-positive strains compared to PSE and reduced the formation of volatile bases significantly. On the day of sensory rejection for CWC, the formation of trimethylamine and total volatile base nitrogen were reduced by 32.27 and 31.85 % in GSE samples and 19.01 and 24.70 % in PSE samples respectively. The dip treatment of GSE increased the shelflife of mackerel up to 15 days, PSE by 12 and 9 days for CWC during ice storage. Therefore, it can be concluded that, GSE can be used as a promising natural preservative and a substitute to the synthetic counterparts.

Cryo-electron microscopic structure of SecA protein bound to the 70S ribosome.

SecA is an ATP-dependent molecular motor pumping secretory and outer membrane proteins across the cytoplasmic membrane in bacteria. SecA associates with the protein-conducting channel, the heterotrimeric SecYEG complex, in a so-called posttranslational manner. A recent study further showed binding of a monomeric state of SecA to the ribosome. However, the true oligomeric state of SecA remains controversial because SecA can also form functional dimers, and high-resolution crystal structures exist for both the monomer and the dimer. Here we present the cryo-electron microscopy structures of Escherichia coli SecA bound to the ribosome. We show that not only a monomeric SecA binds to the ribosome but also that two copies of SecA can be observed that form an elongated dimer. Two copies of SecA completely surround the tunnel exit, providing a unique environment to the nascent polypeptides emerging from the ribosome. We identified the N-terminal helix of SecA required for a stable association with the ribosome. The structures indicate a possible function of the dimeric form of SecA at the ribosome.

Influence of Button mushroom (Agaricus bisporus) on quality and refrigerated storage stability of patties prepared from sutchi catfish (Pangasius hypophthalmus).

The ability of button mushroom (Agaricus bisporus) in changing physical, chemical, microbial and sensory properties of fish patties prepared from sutchi catfish (Pangasius hypophthalmus) was investigated. Two batches of fresh patties were prepared, one batch was treated with 15 % button mushroom (TP) and other batch was a control (CP) without mushroom. The patties were packed in polythene bags and stored under refrigerated condition (6 ± 2 ºC) without adding any preservatives for the estimation of storage stability. The analyses of patties were conducted at regular intervals of 3 days. The results showed that, Peroxide value, Thiobarbituric acid value, Free fatty acids increased significantly in CP at the end of 12 days whereas the TP was within the acceptable limit up to 16 days. Total volatile base nitrogen and Trimethylamine nitrogen also showed a similar trend. The Total plate count and Aerobic spore formers showed an increasing trend in CP when compared to TP. The sensory scores showed that the overall acceptability of CP were lower than TP, which was acceptable even after 16 days of storage. The present study showed that, the quality and storage stability of TP were observed to be in good condition up to 16 days and started deteriorating 20th day onwards, whereas the CP were acceptable only up to 12 days. Therefore it can be recommended that, addition of 15 % of button mushroom to sutchi catfish patty not only increases the nutritional quality but also increases the shelf life of patties under refrigerated storage.

Translation and validation of a Nepalese version of the Psychosocial Impact of Dental Aesthetic Questionnaire (PIDAQ).

OBJECTIVE: The aim of this study was to develop a reliable and valid Nepali version of the Psychosocial Impact of Dental Aesthetic Questionnaire (PIDAQ). DESIGN: Cross-sectional descriptive validation study. SETTINGS: B.P. Koirala Institute of Health Sciences, Dharan, Nepal. METHODS: A rigorous translation process including conceptual and semantic evaluation, translation, back translation and pre-testing was carried out. Two hundred and fifty-two undergraduates, including equal numbers of males and females with an age ranging from 18 to 29 years (mean age: 22·33±2·114 years), participated in this study. Reliability was assessed by Cronbach's alpha coefficient and the coefficient of correlation was used to assess correlation between items and test-retest reliability. The construct validity was tested by factorial analysis. Convergent construct validity was tested by comparison of PIDAQ scores with the aesthetic component of the index of orthodontic treatment needs (IOTN-AC) and perception of occlusion scale (POS), respectively. Discriminant construct validity was assessed by differences in score for those who demand treatment and those who did not. RESULTS: The response rate was 100%. One hundred and twenty-three individuals had a demand for orthodontic treatment. The Nepali PIDAQ had excellent reliability with Cronbach's alpha of 0·945, corrected item correlation between 0·525 and 0·790 and overall test-retest reliability of 0·978. The construct validity was good with formation of a new sub-domain 'Dental self-consciousness'. The scale had good correlation with IOTN-AC and POS fulfilling convergent construct validity. The discriminant construct validity was proved by significant differences in scores for subjects with demand and without demand for treatment. CONCLUSION: To conclude, Nepali version of PIDAQ has good psychometric properties and can be used effectively in this population group for further research.

Structural and Functional Characterization of Obesumbacterium proteus Phytase: A Comprehensive In-Silico Study.

Phytate, also known as myoinositol hexakisphosphate, exhibits anti-nutritional properties and possesses a negative environmental impact. Phytase enzymes break down phytate, showing potential in various industries, necessitating thorough biochemical and computational characterizations. The present study focuses on Obesumbacterium proteus phytase (OPP), indicating its similarities with known phytases and its potential through computational analyses. Structure, functional, and docking results shed light on OPP's features, structural stability, strong and stable interaction, and dynamic conformation, with flexible sidechains that could adapt to different temperatures or specific functions. Root Mean Square fluctuation (RMSF) highlighted fluctuating regions in OPP, indicating potential sites for stability enhancement through mutagenesis. The systematic approach developed here could aid in enhancing enzyme properties via a rational engineering approach. Computational analysis expedites enzyme discovery and engineering, complementing the traditional biochemical methods to accelerate the quest for superior enzymes for industrial applications.

Oxidative desulfurization of fuels using alcohol-based DESs.

The presence of sulfur-containing compounds in fuel oil has become a major global issue due to their release of toxic sulfur dioxide. Hydrodesulfurization is a commonly used method for removing sulfur from fuel. However, new desulfurization techniques have been developed recently as hydrodesulfurization (HDS) is ineffective in removing refractory sulfur, e.g., BT, DBT, 4-MDBT. In this study, a series of deep eutectic solvent (DES) using ChCl, salicylic acid, oxalic acid, citric acid, and adipic acid as hydrogen bond acceptors and MeOH, EtOH, BuOH, EG, DEG, and TEG as hydrogen bond donors on different mole ratios were synthesized and then investigated the efficiency of these DESs in extracting sulfur from model and diesel fuel. Densities, viscosity, refractive index, and FTIR spectra of synthesized DESs were recorded. It also included oxidative desulfurization, which is a promising approach offering high selectivity, mild reaction conditions, low cost, and high efficiency. Hydrogen peroxide was selected as the oxidant in this study due to its excellent performance, commercial availability, and high proportion of active oxygen. [Citric acid: TEG] [1:7] and [adipic acid: TEG] [1:8] were found to be the most effective, removing up to 44.07% and 42.53% sulfur from model oil during single-stage extraction at 30 °C using a solvent-to-feed ratio of 1.0 and was increased to 86.87% and 85.06% using successive extraction up to the fourth stage. On oxidation, extraction efficiencies were reported to be 98.98%, 87.79%, and 56.25% and 96.96%, 81.22%, and 44.51% for model oil containing DBT and diesel 1 and diesel 2 with DES [citric acid: TEG] [1:7] and [adipic acid: TEG] [1:8] respectively at 30 °C using a solvent-to-feed ratio of 1.0. The study found that [citric acid: TEG] [1:7] exhibits better extraction performance in the deep desulfurization of fuels at an extraction temperature of 30 °C.

Insights into Bactericera cockerelli and Candidatus Liberibacter solanacearum interaction: a tissue-specific transcriptomic approach.

The tomato-potato psyllid, Bactericera cockerelli (Sulc), belonging to the Hemiptera order, is an insect pest of solanaceous crops and vectors a fastidious bacterium, Candidatus Liberibacter solanacearum (CLso), the presumptive causal agent of zebra chip and vein greening diseases in potatoes and tomatoes, respectively. The genome of B. cockerelli has been sequenced recently, providing new avenues to elucidate mechanistic insights into pathogenesis in vegetable crops. In this study, we performed RNA-sequencing of the critical psyllid organs (salivary glands and ovaries) involved in CLso pathology and transmission to host plants. Transcriptome analysis revealed differentially expressed genes and organ-specific enrichment of gene ontology (GO) terms related to metabolic processes, response to stress/stimulus, phagocytosis, proteolysis, endocytosis, and provided candidate genes encoding transcription factors (TFs). To examine gene regulatory networks across the psyllid organs under CLso(-) and CLso(+) conditions, we performed weighted gene co-expression network analysis (WGCNA), and unique modules differentiating the psyllid organs were identified. A comparative GO analysis of the unique gene modules revealed functional terms enriched in response to stress, gene regulation, and cell division processes in the ovaries. In contrast, respiration, transport, and neuronal transmission-related GO terms were enriched in the salivary glands. Altogether, this study reveals new insights into tissue-specific expression of the psyllid organs in the absence or presence of CLso bacterium. This knowledge can be leveraged to develop new pest and disease management strategies by delineating the regulatory networks involved in the psyllid-CLso interaction.

Neoadjuvant chemotherapy with weekly paclitaxel and carboplatin followed by chemoradiation in locally advanced cervical carcinoma: a pilot study.

OBJECTIVE: To evaluate role of dose dense neo-adjuvant chemotherapy (NACT) prior to standard concurrent chemo-radiation (CCRT) in locally advanced cervical cancer. METHODS: Between June 2010 and December 2011, 28 patients (median age - 51 years, range, 35 to 67 years) with locally advanced cervical cancer received NACT using paclitaxel (60 mg/m(2)) and carboplatin (AUC-2) weekly for 6 doses. After a mean interval of 15 days (range 7-23 days), the patients then received definitive radiation and concomitant weekly infusion of cisplatin (40 mg/m(2) for 6 doses). Response to concurrent chemo-radiation and toxicity were end points. RESULTS: Following NACT, 67.8% of patients responded; complete (CR) - 2(7.1%), Partial (PR) - 17 (60.7%), stable 7 (25.0%) and 2 patients (7.1%) progressed. 24 of 28 patients received CCRT; 23/24 achieved CR. 22 of 23 complete responders continue to be in CR at a median follow-up of 12 months (range, 7 to 24 months). Grade III/IV neutropenia was the main hematological toxicity seen in 28.5% and 29% of patients, respectively during NACT and CCRT. CONCLUSIONS: Neoadjuvant chemotherapy with dose dense weekly paclitaxel and carboplatin followed by standard CCRT is a feasible approach and is associated with a high response rate in locally advanced cervical cancer.