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Abstract Manual identification of tomato leaf diseases is a time-consuming and laborious process that may lead to inaccurate results without professional assistance. Therefore, an automated, early, and precise leaf disease recognition system is essential for farmers to ensure the quality and quantity of tomato production by providing timely interventions to mitigate disease spread. In this study, we have proposed seven robust Bayesian optimized deep hybrid learning models leveraging the synergy between deep learning and machine learning for the automated classification of ten types of tomato leaves (nine diseased and one healthy). We customized the popular Convolutional Neural Network (CNN) algorithm for automatic feature extraction due to its ability to capture spatial hierarchies of features directly from raw data and classical machine learning techniques [Random Forest (RF), XGBoost, GaussianNB (GNB), Support Vector Machines (SVM), Multinomial Logistic Regression (MLR), K-Nearest Neighbor (KNN)], and stacking for classifications. Additionally, the study incorported a Boruta feature filtering layer to capture the statistically significant features. The standard, research-oriented PlantVillage dataset was used for the performance testing, which facilitates benchmarking against prior research and enables meaningful comparisons of classification performance across different approaches. We utilized a variety of statistical classification metrics to demonstrate the robustness of our models. Using the CNN-Stacking model, this study achieved the highest classification performance among the seven hybrid models. On an unseen dataset, this model achieved average precision, recall, f1-score, mcc, and accuracy values of 98.527%, 98.533%, 98.527%, 98.525%, and 98.268%, respectively. Our study requires only 0.174 s of testing time to correctly identify noisy, blurry, and transformed images. This indicates our approach's time efficiency and generalizability in images captured under challenging lighting conditions and with complex backgrounds. Based on the comparative analysis, our approach is superior and computationally inexpensive compared to the existing studies. This work will aid in developing a smartphone app to offer farmers a real-time disease diagnosis tool and management strategies.

Abstract Background V0v spinal interneurons are highly conserved, glutamatergic, commissural neurons that function in locomotor circuits. We have previously shown that Evx1 and Evx2 are required to specify the neurotransmitter phenotype of these cells. However, we still know very little about the gene regulatory networks that act downstream of these transcription factors in V0v cells. Methods To identify candidate members of V0v gene regulatory networks, we FAC-sorted wild-type and evx1;evx2 double mutant zebrafish V0v spinal interneurons and expression-profiled them using microarrays and single cell RNA-seq. We also used in situ hybridization to compare expression of a subset of candidate genes in evx1;evx2 double mutants and wild-type siblings. Results Our data reveal two molecularly distinct subtypes of zebrafish V0v spinal interneurons at 48 h and suggest that, by this stage of development, evx1;evx2 double mutant cells transfate into either inhibitory spinal interneurons, or motoneurons. Our results also identify 25 transcriptional regulator genes that require Evx1/2 for their expression in V0v interneurons, plus a further 11 transcriptional regulator genes that are repressed in V0v interneurons by Evx1/2. Two of the latter genes are hmx2 and hmx3a. Intriguingly, we show that Hmx2/3a, repress dI2 interneuron expression of skor1a and nefma, two genes that require Evx1/2 for their expression in V0v interneurons. This suggests that Evx1/2 might regulate skor1a and nefma expression in V0v interneurons by repressing Hmx2/3a expression. Conclusions This study identifies two molecularly distinct subsets of zebrafish V0v spinal interneurons, as well as multiple transcriptional regulators that are strong candidates for acting downstream of Evx1/2 to specify the essential functional characteristics of these cells. Our data further suggest that in the absence of both Evx1 and Evx2, V0v spinal interneurons initially change their neurotransmitter phenotypes from excitatory to inhibitory and then, later, start to express markers of distinct types of inhibitory spinal interneurons, or motoneurons. Taken together, our findings significantly increase our knowledge of V0v and spinal development and move us closer towards the essential goal of identifying the complete gene regulatory networks that specify this crucial cell type.

Immunotherapy, particularly targeting the PD-1/PD-L1 pathway, holds promise in cancer treatment by regulating the immune response and preventing cancer cells from evading immune destruction. Nonetheless, this approach poses a risk of unwanted immune system activation against healthy cells. To minimize this risk, our study proposes a strategy based on selective targeting of the PD-L1 pathway within the acidic microenvironment of tumors. We employed in silico methods, such as virtual screening, molecular mechanics, and molecular dynamics simulations, analyzing approximately 10,000 natural compounds from the MolPort database to find potential hits with the desired properties. The simulations were conducted under two pH conditions (pH = 7.4 and 5.5) to mimic the environments of healthy and cancerous cells. The compound MolPort-001-742-690 emerged as a promising pH-selective inhibitor, showing a significant affinity for PD-L1 in acidic conditions and lower toxicity compared to known inhibitors like BMS-202 and LP23. A detailed 1000 ns molecular dynamics simulation confirmed the stability of the inhibitor-PD-L1 complex under acidic conditions. This research highlights the potential of using in silico techniques to discover novel pH-selective inhibitors, which, after experimental validation, may enhance the precision and reduce the toxicity of immunotherapies, offering a transformative approach to cancer treatment.

We present observations, numerical simulations, and analysis from experiments in the Lithium Tokamak Experiment-Beta (LTX- β ) in which the electron temperature profile ( T _e ( r )) shifts from flat to peaked and a tearing mode is also destabilized when the average density ( n _e ^ave ) exceeds ∼10 ^19 m ^−3 . Flat T _e ( r ) is obtained routinely in LTX- β , with a lithium coated, low-recycling first wall, once the external fueling is stopped and density decays [Boyle et al 2023 Nucl. Fusion 63 056020]. In the present experiment, flat T _e profiles can be sustained while maintaining constant n _e ^ave below a line averaged density threshold ( n _e ^ave _th ) of ∼10 ^19 m ^−3 . Above n _e ^ave _th , T _e ( r ) shifts from flat to peaked and a tearing mode is destabilized. Due to low recycling, the achieved n _e ^ave can be controlled precisely by external fueling and hence, a certain threshold of the edge neutral inventory from the external fueling is experimentally manifested through n _e ^ave _th . The goal of the present work is to investigate the role of edge neutrals in determining T _e ( r ) and MHD stability in the unique low-recycling regime of LTX- β . Our hypothesis is that the peaking of T _e ( r ) beyond n _e ^ave _th is due ultimately to the edge cooling by the cold neutrals beyond a critical fueling flux. At lower fueling flux, flat T _e ( r ) results in broader pressure profile and lower resistivity, which in turn stabilizes the tearing mode. This hypothesis is supported by edge neutral density estimation by DEGAS 2 code. Mode analysis by singular value decomposition confirms the tearing mode structure to be m / n = 2/1 ( m and n being the poloidal and toroidal mode numbers). Linear tearing stability analysis with M3D-C1 predicts that plasmas with n _e ^ave > 10 ^19 are highly susceptible to a n = 1 tearing mode. ORBIT simulations, however, confirmed that the tearing modes do not contribute to the loss of fast ions from neutral beam injection. This study shows for the first time that the neutral inventory at the edge could be one of the deciding factors for the achievability of the unique operation regime of flat T _e ( r ) and the excitation of tearing activity that could be disruptive for the plasmas.

The edge localized mode (ELM) frequency ( f _ELM ) decreased by 63% when electron cyclotron heating (ECH) deposition location is shifted from ρ = 0.4 to ρ = 0.8 in DIII-D discharges where the power ratio between neutral beam injection (NBI) and ECH ( P _NBI / P _ECH ) is kept at ∼1. The performance of the pedestal in the ECH heated case is compared with a pure NBI reference discharge while keeping the total input power constant. All these discharges are performed at balanced input torque conditions. Furthermore, in the pure NBI discharge a strong decoupling of the peeling–ballooning (PB) thresholds is observed. The PB decoupling is preserved when the ECH is deposited at ρ = 0.8 and P _NBI / P _ECH ∼ 1, while the thresholds manifest a closed stability boundary when the ECH is deposited at ρ = 0.4. The inter-ELM pedestal recovery time is considerably larger for the ECH at ρ = 0.8 case. Increased pedestal turbulence is observed in beam emission spectroscopy (BES), Doppler backscattering and magnetic diagnostics for the ECH at the ρ = 0.8 case. Strong growth of a TEM-like mode is observed in BES and the mode growth is correlated with the decrease in f _ELM . In view of these observations, the increased pedestal turbulence seems to be the plausible reason behind the delayed pedestal recovery following an ELM event in the ECH at ρ = 0.8 case, and the preservation of PB decoupling through temperature pedestal profile widening. TRANSP interpretative simulations show that the ECH at the ρ = 0.8 case is more susceptible to ITG/TEM turbulence.

Here the authors show that reverse weathering reactions, such as the formation of glauconite minerals, are first-order controls on element sequestration in shallow marine sediments throughout Earth history, in particular during greenhouse periods with sea level highstand.

Obesity causes chronic inflammation and changes in gut microbiome. However, how this contributes to poor survival and therapy resistance in patients with pancreatic cancer remain undetermined. Our current study shows that high fat diet-fed obese pancreatic tumor bearing mice do not respond to standard of care therapy with gemcitabine and paclitaxel when compared to corresponding control diet-fed mice. C57BL6 mice were put on control and high fat diet for 1 month following with pancreatic tumors were implanted in both groups. Microbiome of lean (control) and obese (high fat diet fed) mice was analyzed. Fecal matter transplant from control mice to obese mice sensitized tumors to chemotherapy and demonstrated extensive cell death. Analysis of gut microbiome showed an enrichment of queuosine (Q) producing bacteria in obese mice and an enrichment of S-adenosyl methionine (SAM) producing bacteria in control diet-fed mice. Further, supplementation of obese animals with SAM sensitized pancreatic tumors to chemotherapy. Treatment of pancreatic cancer cells with Q increased PRDX1 involved in oxidative stress protection. In parallel, tumors in obese mice showed increase in CD133+ treatment refractory tumor populations compared to control animals. These observations indicated that microbial metabolite Q accumulation in high fat diet-fed mice protected tumors from chemotherapy induced oxidative stress by upregulating PRDX1. This protection could be reversed by treatment with SAM. We conclude that relative concentration of SAM and queuosine in fecal samples of pancreatic cancer patients can be developed as a potential biomarker and therapeutic target in chemotherapy refractory pancreatic cancer.

The late Paleocene–early Eocene warm greenhouse conditions, characterized by elevated pCO2 levels in the atmosphere and a dramatic increase in sea surface temperature, prompted abundant authigenic glauconite formation within the shallow marine sediments worldwide by lowering the net sedimentation rate, increasing organic productivity and expanding the oxygen minimum zones to shallow oceans. The early Eocene marginal marine Cambay Shale Formation experienced episodes of marine inundation represented by limestone–green shale alternations. The shales host abundant authigenic light-green, dark-green, and brown pellets. A detailed characterization of the pellets of the Valia and Vastan lignite mines, integrating the sedimentological, petrographical, mineralogical, and mineral geochemical data, suggests two distinct varieties of Fe–silicate formation, viz. glauconite and chamosite. While the glauconitic green pellets are ubiquitous to Valia and Vastan mines, brown chamosite pellets are confined within the basal part of the green shale facies alternating with fossiliferous limestone in the Vastan mine. The glauconites of the Valia mine manifest a ‘nascent’ to ‘slightly evolved’ maturation stage of glauconitization, whereas the glauconites of the Vastan mine represent the ‘evolved’ type. The limestone–green shale alternation in the Valia mine is overlain by a ~4 m-thick spherulitic mudstone facies comprising monomineralic sideritic spherulites, reflecting a pure FeCO3 composition. The glauconites in the Cambay Shale Formation transformed from kaolinite-rich clay pellets under dys-oxic depositional conditions. The increasing anoxicity within the microenvironment, possibly amplified by the rapid oxidation of continent-derived organic matter, facilitated chamosite formation instead of glauconite. The increased freshwater influx into the marginal marine depositional environment resulted in immature, K-poor glauconites of the Valia mine. The formation of siderite spherulites overlying the limestone–green shale alternation relates to the beginning of the regressive phase of sedimentation.

Background: Gestational Diabetes Mellitus (GDM) is a public health problem in India with implications well pronounced in pregnancy and beyond. Biomarkers like Glycated Albumin (G.A.) can well monitor the glycaemic status and evaluate the transient hyperglycaemic spikes, which account for the diabetic complications. Aims and Objectives: In this study, we intend to study urinary G.A. excretion with respect to urinary albumin excretion expressed as UGA% in gestational diabetes mellitus. Materials and Methods: A prospective observational study was conducted for a period of 16 months on 177 pregnant women who attended antenatal clinics for the first time at a single centre.Among the surveyed population, 26 pregnant women subsequently developed GDM, and 31 healthy pregnant women who did not develop GDM were included in the study. Results: The UGA% between GDM and healthy mothers showed an increase in GDM with a p value

Background: Paucity of literature and non consensus on clinicohistopathological features amongst the nonmelasma facial melanosis for example lichen planus pigmentosus (LPP), pigmented contact dermatitis (PCD), macular amyloidosis, acanthosis nigricans, pigmented demarcation line, post inflammatory hyperpigmentation, etc., make them difficult to diagnose and equally challenging to treat. Materials and Methods: It was a prospective, uncontrolled study, conducted at tertiary hospital at eastern India in 100 patients presenting with facial hyperpigmentation who agreed to undergo 3 mm skin biopsy during Jan 2014 to Jun 2015. Cases of melasma were excluded by clinical, Woods lamp examination and if required dermoscopy. Details of history, physical examination, histopathological examination, and Immunohistochemical studies were recorded. Melan A was used as melanocytic differentiation marker while CD4, CD8 were used as inflammatory markers. Mean ± SD, chi-square test or Fisher’s exact test, degree of agreement by Cohen’s Kappa were calculated. P-value was considered significant if ≤0.05. Results: 44 males and 56 females (56%) (M: F=1:1.24) with mean age of 45.98 years and median duration of illness of 28 months (5 months-13 years) were studied. Out of 43 confirmed cases of PCD, 16 had associated hypothyroidism (chi square 6.11, P-value 0.0134). Maximum patients belonged PCD (n = 47) followed by LPP (n = 27). Maximum concordance of clinical and histopathological diagnosis was present in PCD and LPP (Cohen kappa more than 0.9). Epidermal atrophy and band like inflammatory infiltrate were statistically significant features in LPP (P < 0.001). There was no histopathological and immunohistochemical correlation. Overall, clinical histopathological concordance rate was 77%. Conclusion: Subset of nonmelasma facial melanosis is difficult to diagnose clinically which require further confirmation by histopathological examination. Small number of patients in other groups apart from PCD and LPP and uncontrolled study were major limitations of this study.

Abstract Although Paleogene warm climatic intervals have received considerable attention for atmospheric and oceanographic changes, the authigenic mineralization associated with these time spans remains overlooked. An extensive review of the literature reveals a close correspondence between the high abundance of glauconite and warm climatic intervals during the Paleogene period. The abundance of phosphorite, ironstone, lignite and black shale deposits reveals similar trends. Although investigated thoroughly, the origin of these authigenic deposits is never understood in the background of Paleogene warming climatic intervals. A combination of factors like warm seawater, hypoxic shelf, low rate of sedimentation, and enhanced rate of continental weathering facilitated the glauconitization. The last factor caused the excess supply of nutrients, including Fe, Si, K, Mg and Al through the rivers, the cations needed for the formation of glauconite. The excessive inflow of nutrient-rich freshwater into the shallow seas further ensured high organic productivity and stratification in shallow shelves, causing hypoxia. The consequent rapid rise in sea-level during the warm periods created extensive low-relief shallow marine shelves starved in sediments. Oxygen-deficiency in the shallow marine environment facilitated the fixation of Fe into the glauconite structure. The inflow of nutrient-rich water during the warm climatic intervals facilitated the formation of phosphorite, ironstone, and organic-matter-rich sedimentary deposits as well. Although global factors primarily controlled the formation of these authigenic deposits, local factors played significant roles in some of the deposits. Therefore, phosphorites formed in marine conditions with open circulation within the tropical zone. While lush growth of rainforest covers in the tropical belt facilitated the formation of coastal lignite.

Abstract Background Autoimmune diseases have been associated with changes in the gut microbiome. In this study, the gut microbiome was evaluated in individuals with dry eye and bacterial compositions were correlated to dry eye (DE) measures. We prospectively included 13 individuals with who met full criteria for Sjögren’s (SDE) and 8 individuals with features of Sjögren’s but who did not meet full criteria (NDE) for a total of 21 cases as compared to 21 healthy controls. Stool was analyzed by 16S pyrosequencing, and associations between bacterial classes and DE symptoms and signs were examined. Results Results showed that Firmicutes was the dominant phylum in the gut, comprising 40–60% of all phyla. On a phyla level, subjects with DE (SDE and NDE) had depletion of Firmicutes (1.1-fold) and an expansion of Proteobacteria (3.0-fold), Actinobacteria (1.7-fold), and Bacteroidetes (1.3-fold) compared to controls. Shannon’s diversity index showed no differences between groups with respect to the numbers of different operational taxonomic units (OTUs) encountered (diversity) and the instances these unique OTUs were sampled (evenness). On the other hand, Faith’s phylogenetic diversity showed increased diversity in cases vs controls, which reached significance when comparing SDE and controls (13.57 ± 0.89 and 10.96 ± 0.76, p = 0.02). Using Principle Co-ordinate Analysis, qualitative differences in microbial composition were noted with differential clustering of cases and controls. Dimensionality reduction and clustering of complex microbial data further showed differences between the three groups, with regard to microbial composition, association and clustering. Finally, differences in certain classes of bacteria were associated with DE symptoms and signs. Conclusions In conclusion, individuals with DE had gut microbiome alterations as compared to healthy controls. Certain classes of bacteria were associated with DE measures.

Abstract Resistance to therapy is one of the major factors that contribute to dismal survival statistics in pancreatic cancer. While there are many tumor intrinsic and tumor microenvironment driven factors that contribute to therapy resistance, whether pre-existing metabolic diseases like type 2 diabetes (T2D) contribute to this has remained understudied. It is well accepted that hyperglycemia associated with type 2 diabetes changes the gut microbiome. Further, hyperglycemia also enriches for a “stem-like” population within the tumor. In the current study, we observed that in a T2D mouse model, the microbiome changed significantly as the hyperglycemia developed in these animals. Our results further showed that, tumors implanted in the T2D mice responded poorly to gemcitabine/paclitaxel (Gem/Pac) standard of care compared to those in the control group. A metabolomic reconstruction of the WGS of the gut microbiota further revealed that an enrichment of bacterial population involved in drug metabolism in the T2D group. Additionally, we also observed an increase in the CD133+ tumor cells population in the T2D model. These observations indicated that in an animal model for T2D, microbial dysbiosis is associated with increased resistance to chemotherapeutic compounds.

Abstract This study investigates the process of formation of ooidal ironstones in the Upper Cretaceous-Paleogene succession in western Siberia. The formation of such carbonate-based ironstones is a continuing problem in sedimentary geology, and in this study, we use a variety of data and proxies assembled from core samples to develop a model to explain how the ooidal ironstones formed. Research on pyrite framboids and geochemical redox proxies reveals three intervals of oceanic hypoxia during the deposition of marine ooidal ironstones in the Late Cretaceous to the Early Paleogene Bakchar ironstone deposit in western Siberia; the absence of pyrite indicates oxic conditions for the remaining sequence. While goethite formed in oxic depositional condition, chamosite, pyrite and siderite represented hypoxic seawater. Euhedral pyrite crystals form through a series of transition originating from massive aggregate followed by normal and polygonal framboid. Sediments associated with goethite-chamosite ironstones, encompassing hypoxic intervals exhibit positive cerium, negative europium, and negative yttrium anomalies. Mercury anomalies, associated with the initial stages of hypoxia, correlate with global volcanic events. Redox sensitive proxies and ore mineral assemblages of deposits reflect hydrothermal activation. Rifting and global volcanism possibly induced hydrothermal convection in the sedimentary cover of western Siberia, and released iron-rich fluid and methane in coastal and shallow marine environments. This investigation, therefore, reveals a potential geological connection between Large Igneous Provinces (LIPs), marine hypoxia, rifting and the formation of ooidal ironstones in ancient West Siberian Sea.

Aging is associated with declining immunity and inflammation as well as alterations in the gut microbiome with a decrease of beneficial microbes and increase in pathogenic ones. The aim of this study was to investigate the age associated gut microbiome in relation to immunologic and metabolic profile in a non-human primate (NHP) model. 12 geriatric (age 19-24 years) and 4 young adult (age 3-4 years) Rhesus macaques were included in this study. Immune cell subsets were characterized in peripheral blood mononuclear cells (PBMC) by flow cytometry and plasma cytokines levels were determined by bead based multiplex cytokine analysis. Stool samples were collected by ileal loop and investigated for microbiome analysis by shotgun metagenomics. Serum, gut microbial lysate, and microbe-free fecal extract were subjected to metabolomic analysis by mass-spectrometry. Our results showed that the gut microbiome in geriatric animals had higher abundance of Archaeal and Proteobacterial species and lower Firmicutes than the young adults. Highly abundant microbes in the geriatric animals showed a direct association with plasma biomarkers of inflammation and immune activation such as neopterin, CRP, TNF, IL-2, IL-6, IL-8 and IFN-γ. Significant enrichment of metabolites that contribute to inflammatory and cytotoxic pathways was observed in serum and feces of geriatric animals compared to the young adults. We conclude that aging NHP undergo immunosenescence and age associated alterations in the gut microbiome that has a distinct metabolic profile. Aging NHP can serve as a model for investigating the relationship of the gut microbiome to particular age-associated comorbidities and for strategies aimed at modulating the microbiome.

The approximately 2 km thick fluvio-lacustrine deposits of Pranhita-Godavari Gondwana syn-rift basin, ranging in age from 235 to 196 Ma, track the compositional changes from the Middle Triassic to Early Jurassic. Mineralogical and geochemical investigations, as well as paleocurrent data of the siliciclastic deposits of the four conformable formations—Yerrapalli, Bhimaram, Maleri and Dharmaram—trace the source of sediments to the south and southwest of the Gondwana basin. The dominance of arkosic to sub-arkosic sandstones in all the formations suggests mostly felsic sources. The high value of Zr/Sc, as well a high content of Hf, reflects the addition of zircon by sediment recycling. The index of compositional variability (ICV) and chemical index of alteration (CIA) values of these Gondwana samples suggest intermediate weathering of Proterozoic shales, granites and gneisses. The concentration of Cr and Ni, ratios of Eu/Eu* and (GdN/YbN) suggest a dominant post-Archean source. The insignificant variation in ICV and CIA values across the studied Mesozoic formations corroborates the continuation of syn-rift tectonics of the Pranhita-Godavari Gondwana basin since the Late Paleozoic. Sandstone samples show a gradual shift from arkose to subarkose in Yerrapalli, Barakar and Maleri formations, and to sublithic arenite sandstones in the younger Dharmaram formation, indicating recycling. However, the insignificant variation of feldspar and/or quartz content throughout these Mesozoic formations suggests lesser tectonic activity. The paleocurrent direction, shifting from NNW to NE direction, suggests a change in basin tectonism and/or sediment supply, which is corroborated by mineralogical and geochemical data.

Green authigenic mica, i.e., celadonite, is commonly associated with submarine alteration of basic igneous rock. However, very few studies have reported the formation of celadonite under nonmarine conditions. An integrated study involving field investigation, petrography, mineralogy, and mineral chemistry highlighted the origin of celadonite in two clay-rich horizons (green boles) of the Late Cretaceous Deccan volcanic province. Within the Salher green bole, the celadonite occurred as the dissolution and alteration of plagioclase, volcanic glass, and pore-filling cement. In the case of the Pune green bole, the celadonite was formed by the alteration of plagioclase, pyroxene, and precipitation as film within intergranular pores, along with zeolite. The celadonite in the Salher green bole exhibited slightly lower K2O and Fe2O3 and higher Al2O3 than in the Pune. The mineral chemistry of the former showed a composition closer to ferro-aluminoceladonite. Although the mineral chemistry of celadonite overlaps with glauconite, the distinct 10 Å and 15 Å reflections in XRD, euhedral lath and honeycomb morphology under SEM, and characteristic absorption bands in VNIR spectroscopy (0.4–2.5 µm) and FTIR spectroscopy (400–4000 cm−1) identified celadonite and Fe-smectite within green boles. The green boles were formed either by the alteration of a volcaniclastic deposit in local pools of water or by the in situ alteration of the fragmentary flow top. The present study is significant due to the occurrence of celadonite in a nonmarine environment, as it otherwise forms under submarine conditions.

This research presents the mechanical creation of smart fertilizers from a mixture of smectite and urea in a 3:2 ratio by using the planetary milling technique. The smectite–urea composites show intercalation between urea and mineral, which increases steadily with increasing activation time. A shift of X-Ray Diffraction basal reflections, intensities of Fourier transform infrared spectroscopy (FTIR) peaks, and weight losses in thermogravimetric analysis (TG) document the systematic crystallo-chemical changes of the composites related to nitrogen interaction with activation. Observations of the nanocomposites by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) corroborate the inference. Nitrogen intercalates with smectite in the interlayer space and remains absorbed either within micro-aggregates or on the surface of activated smectites. Soil leaching tests reveal a slower rate of nitrogen than that of traditional urea fertilizers. Different forms of nitrogen within the composites cause their differential release rates to the soil. The formulated nanocomposite fertilizer enhances the quality and quantity of oat yield.

Intestinal barrier dysfunction and subsequent microbial translocation play crucial roles in persistent immune activation leading to HIV disease progression. Opioid use is associated with worse outcome in HIV-infected patients. The exacerbated disease progression by opioids is mainly driven by excessive intestinal inflammation and increased gut permeability. The objective of this study is to investigate how opioids potentiate HIV disease progression by compromising intestinal barrier function and impairing intestinal epithelial self-repair mechanism. In the present study, abnormal intestinal morphology and reduced epithelial proliferation were observed in bone marrow-liver-thymus humanized mice and in HIV-infected patients who were exposed to opioids. In bone marrow-liver-thymus mice, HIV, and morphine independently, and additively induced gut dysbiosis, especially depletion of Lachnospiraceae, Ruminococcaceae, and Muribaculaceae. We also observed that the abundance of Lachnospiraceae, Ruminococcaceae, and Muribaculaceae negatively correlated with apoptosis of epithelial cells, and intestinal IL-6 levels. Previous studies have shown that these bacterial families play crucial roles in maintaining intestinal homeostasis because they include most short-chain fatty acid-producing members. Short-chain fatty acids have been shown to maintain stem cell populations and suppress inflammation in the gut by inhibiting histone deacetylases (HDAC). In addition, we demonstrate that morphine exposure inhibited growth of intestinal organoids derived from HIV transgenic mice by suppressing Notch signaling in an HDAC-dependent manner. These studies implicate an important role for HDAC in intestinal homeostasis and supports HDAC modulation as a therapeutic intervention in improving care of HIV patients, especially in opioid-abusing population.

Abstract This paper investigates the provenance of Middle Jurassic to Early Cretaceous sediments in the Kutch Basin, western India, on the basis of mineralogical investigations of sandstones composition (Quartz–Feldspar–Lithic (QFL) fragment), Zircon–Tourmaline–Rutile (ZTR) index, and mineral chemistry of heavy detrital minerals of the framework. The study also examines the compositional variation of the sandstone in relation to the evolution of the Kutch Basin, which originated as a rift basin during the Late Triassic and evolved into a passive margin basin by the end Cretaceous. This study analyzes sandstone samples of Jhumara, Jhuran and Bhuj Formations of Middle Jurassic, Upper Jurassic and Lower Cretaceous, respectively, in the Kutch Mainland. Sandstones record a compositional evolution from arkosic to subarkosic as the feldspar content decreases from 68% in the Jhumara Formation to 27% in the Bhuj Formation with intermediate values in the Jhuran Formation. The QFL modal composition indicates basement uplifted and transitional continental settings at source. Heavy mineral content of these sandstones reveals the occurrence of zircon, tourmaline, rutile, garnet, apatite, monazite and opaque minerals. Sub-rounded to well-rounded zircon grains indicate a polycyclic origin. ZTR indices for samples in Jhumara, Jhuran and Bhuj Formations are 25%, 30% and 50% respectively. Chemistry of opaque minerals reveals the occurrence of detrital varieties such as ilmenite, rutile, hematite/magnetite and pyrite, in a decreasing order of abundances. Chemistry of ilmenites in the Jhumara Formation reveals its derivation from dual felsic igneous and metabasic source, while those in Jhuran and Bhuj Formations indicate a metabasic derivation. Chemistry of garnet reveals predominantly Fe-rich (almandine) variety of metabasic origin. X-ray microscopic study provides the percentage of heavy minerals ranging from 3% to 5.26%. QFL detrital modes reflect the evolution of the basin from an active rift to a passive margin basin during the Mesozoic. Integration of results from QFL modal composition of the sandstones, heavy mineral analysis and mineral chemistry, suggests sediment supply from both northern and eastern highlands during the Middle Jurassic. The uplift along the Kutch Mainland Fault in the Early Cretaceous results in curtailment of sediment input from north.

This study presents geochemical characteristics of glauconites in estuarine deposits within the Maastrichtian Lameta Formation in central India. Resting conformably over the Bagh Group, the Lameta Formation consists of ∼4–5 m thick arenaceous, argillaceous and calcareous green sandstones underlying the Deccan Traps. The sandstone is friable, medium- to coarse-grained, well-sorted and thoroughly cross-stratified, and contains marine fossils. Detailed petrography, spectroscopy and mineral chemistry indicates unique chemical composition of glauconite with high K2O, MgO, Al2O3 and moderate TFe2O3. Glauconite is formed by the replacement of K-feldspars, initially as stringers in the cleavages and fractures of feldspars. Incipient glauconite subsequently evolves fully, appearing as pellets. Fully-evolved glauconite pellets often leave tiny relics of K-feldspar. XRD exhibits characteristic peak of 10 Å from basal (001) reflection of glauconite, indicating the “evolved” character. The K2O content of glauconites in the Lameta Formation varies from 5.51% to 8.29%, corroborating the “evolved” to “highly-evolved” maturation stage. The TFe2O3 content of glauconite varies from 12.56% to 18.90%. The PASS-normalized-REE patterns of glauconite exhibit a “hat-shape” confirming the authigenic origin of glauconites. The slightly-negative to slightly-positive Ce anomaly value and the moderate TFe2O3 content of glauconite agree well with a suboxic, estuarine condition. The replacement of K-feldspar by the glauconite contributes towards the high K2O content. Compositional evolution of glauconites in the Lameta Formation is similar to those observed in many Precambrian sedimentary sequences. Keywords: Glauconite, Estuary, Mineral chemistry, Cerium anomaly, Redox condition, Lameta Formation, Narmada Basin

Middle Eocene Fulra Limestone and Oligocene Maniyara Fort Formation represent platform carbonate deposits of Kutch at the north-western margin of India. These carbonates contain larger benthic foraminifera, including Alveolina, Assilina, Discocyclina, Lepidocyclina, Miogypsina, Nummulites and Spiroclypeus. This study presents paleodepositional and paleobathymetric interpretations for both formations using benthic foraminifera in combination with lithological association, sedimentary structures and early diagenetic features. The six carbonate facies comprising the Fulra Limestone indicate a depositional spectrum ranging from bar-lagoon to mid-ramp depositional conditions. It records several shallowing upward cycles, leading to emergence and formation of paleokarst. The four carbonate facies of the Maniyara Fort Formation represents deposition within the inner ramp setting in bar-lagoon and patch-reef environment, while intervening fine siliciclastics correspond to episodes of relative sea level fall. Nummulitic accumulations form low-relief bars within the fair weather wave base in both the formations. The depositional setting of the Paleogene carbonate in Kutch broadly resembles Eocene platformal deposits in the circum-Tethys belt.

The Paleogene sections of Kutch are the reference for the regional chronostratigraphic units of India. The ages of these dominantly shallow marine carbonates are mainly based on larger benthic foraminifera (LBF). The taxonomic revisions of the LBF and the progressively refined shallow benthic zonations (SBZ) have necessitated the present study on updating the stratigraphy of the area. The sedimentation in Kutch commenced with the deposition of volcaniclastics in terrestrial environments in the Paleocene. The marine transgression in SBZ 5/6 deposited finer clastics and carbonates, designated as Naredi Formation, in early Eocene. There is no evidence of marine Paleocene in Kutch. A major hiatus spanning SBZ 12 to SBZ 16 was followed by the development of a carbonate platform and deposition of Harudi Formation – Fulra Limestone during the Bartonian, SBZ 17. The hiatus corresponds to a widespread stratigraphic break in Pakistan and India to Australia, referred as the ‘Lutetian Gap.’ The Maniyara Fort Formation is assigned to SBZ 22 B and SBZ 23, and its age is revised to Chattian. Climate played a major role in building up of the Paleogene stratigraphic succession of Kutch, the carbonates formed during the warming intervals and the stratigraphic gaps were in the intervening cooling periods.

The roughly 6 m thick limestone–green shale alternation within the lignite-bearing Giral Member of the Barmer Basin corresponds to a marine flooding event immediately after the Paleocene–Eocene transition. A detailed characterization of the glauconite using Electron Probe Micro Analyzer (EPMA), X-Ray Diffraction (XRD), Mössbauer and Field Emission Gun-Scanning Electron Microscope (FEG-SEM) reveals its origin in the backdrop of prevailing warm climatic conditions. The glauconite pellets vary from fine silt-sized to coarse sand-sized pellets, often reaching ~60% of the rock by volume. Mineralogical investigation reveals a ‘nascent’ to ‘slightly evolved’ character of the marginal marine-originated glauconite showing considerable interstratification. The chemical composition of the glauconite is unusual with a high Al2O3 (>10 wt%) and moderately high Fe2O3(total) contents (>15 wt%). While the K2O content of these glauconites is low, the interlayer sites are atypically rich in Na2O, frequently occupying ~33% of the total interlayer sites. The Mössbauer spectrum indicates 10% of the total iron is in ferrous form. High tetrahedral Al3+ of these glauconites suggests a high-alumina substrate that transformed to glauconite by octahedral Al-for-Fe substitution followed by the addition of K into the interlayer structure. The unusually high Na2O suggests the possibility of a soda-rich pore water formed by the dissolution of alkaline volcanic minerals. The Giral glauconite formation could have been a part of the major contributors in the Fe-sequestration cycle in the Early Eocene shelves. Warm climate during the Early Eocene time favored the glauconitization because of the enhanced supply of Fe, Al, and Si and proliferation of an oxygen-depleted depositional environment.

This study reconstructs the depositional conditions of ironstones within the Chulym-Yenisey basin and assesses the iron source. The detrital minerals of the studied deposits include quartz and feldspar. The authigenic minerals are goethite, siderite, aragonite, dolomite, calcite, apatite, barite, and pyrite. The clay components include minerals of the chlorite group (possible chamosite), nontronite, kaolinite, illite, and beidellite. Local bacterial sulfate reduction led to the formation of pyrite framboids in siltstone layers. The subsequent diagenetic iron reduction promoted the formation of chamosite from siderite. The goethite precipitation occurred in an oxidic aqueous environment. The Cretaceous continental sediments of the Ilek and Kia Formations of the Chulym-Yenisei depression consist of fine- and medium-grained, cross-stratified, poorly sorted litho-feldspatho-quartzose sandstones of fluvial channel origin alternating with bluish-gray siltstones and ironstones of floodplain–lacustrine–bog origin. Thin layers of iron-bearing rocks within siltstones formed in meromictic waters. The changes in geochemical proxies demonstrate fluctuations of paleoenvironmental conditions within the Cretaceous sequence. Siltstones and sandstones formed under humid and arid conditions, respectively. The primary iron source for sediments of the Chulym-Yenisey depression was determined as volcanogenic and igneous rocks of the Altai-Sayan mountainous region.

This study presents a review on palaeogeographic implications and temporal variations of glaucony covering both modern and ancient records. Phanerozoic glaucony preferably forms in a shelf depositional setting. Deep marine conditions and low seawater temperature discourage formation of glaucony. Around 75% of glaucony is recorded from the Cretaceous to the Holocene sediments, which are related to the abundance of the most common substrates, faecal pellets and bioclasts. TFe2O3 (total), Al2O3, K2O and MgO contents of glaucony vary appreciably through geological time. While TFe2O3 content of most Mesozoic and Cenozoic glaucony exceeds 20%, it is always less than 20% in Precambrian varieties. High K2O, Al2O3, MgO and low TFe2O3 distinguish the Precambrian glaucony from its Phanerozoic counterpart. Precambrian glaucony, preferably formed within a K-feldspar substrate, is always rich in potassium irrespective of its degree of evolution, while high K-content in Phanerozoic evolved glaucony indicates significant stratigraphic condensation. K2O vs. TFe2O3 relationship of glaucony exhibits three different evolutionary trends corresponding to three common modes of origin. Depositional conditions may influence the composition of glaucony as slightly reducing conditions favour Fe enrichment, whereas oxidising conditions cause Fe depletion in glaucony.

Cigarette smoke (CS) is an important source of morbidity and early mortality worldwide. Besides causing various life-threatening diseases, CS is also known to cause hypoxia. Chronic hypoxia would induce early aging and premature death. Continuation of smoking during pregnancy is a known risk for the unborn child. Although carbon monoxide (CO) is considered to be a cause of hypoxia, the effect of other component(s) of CS on hypoxia is not known. Here we show by immunoblots and mass spectra analyses that in smoker’s blood p-benzoquinone (p-BQ) derived from CS forms covalent adducts with cysteine 93 residues in both the β chains of hemoglobin (Hb) producing Hb-p-BQ adducts. UV–vis spectra and CD spectra analyses show that upon complexation with p-BQ the structure of Hb is altered. Compared to nonsmoker’s Hb, the content of α-helix decreased significantly in smoker’s Hb (p = 0.0224). p-BQ also induces aggregation of smoker’s Hb as demonstrated by SDS-PAGE, dynamic light scattering and atomic force microscopy. Alteration of Hb structure in smoker’s blood is accompanied by reduced oxygen binding capacity. Our results provide the first proof that p-BQ is a cause of hypoxia in smokers. We also show that although both p-BQ and CO are responsible for causing hypoxia in smokers, exposure to CO further affects the function over and above that produced by Hb-p-BQ adduct. Keywords: p-Benzoquinone, Human smoker’s hemoglobin, Mass spectrometry, Atomic force microscopy, Oxygen binding capacity, CORM-3 [tricarbonylchloro(glycinato)ruthenium(II)]

This study explores the fertilizer potential of glauconitic soil by monitoring its impact on the growth of plants during the second growing season after application. Our study documents a higher growth of oats (Avena sativa) in glauconitic amended soil compared to that recorded with the control sample at the end of a 97-day-long experiment. Concentrations of nutrients (K, P, ammonium, Ca, Mg) and pH of the soil increase sharply in the first growing season and mildly thereafter, after an initial concentration of 200 g·m−2 glauconite (equivalent to 2 t·ha−1). The pH of the glauconitic-amended soil increases from an initial 6.0 to 6.34 during the second season. Organic matter and nitrates decrease in the soil mixture at the end of the second growing season, while the exchangeable ammonium increases. Organic acids promote the mobility and bioavailability of nutrients in the soil. Glauconitic soil is particularly effective for weakly acidic soils with a low moisture content. The steady increase in total yield and plant height, and the slow-release of nutrients during the second growing season indicates that glauconitic soil can be an effective and eco-friendly fertilizer.

Vertebrate locomotor circuitry contains distinct classes of ventral spinal cord neurons which each have particular functional properties. While we know some of the genes expressed by each of these cell types, we do not yet know how several of these neurons are specified. Here, we investigate the functions of Tal1, Gata2a, and Gata3 transcription factors in the development of two of these populations of neurons with important roles in locomotor circuitry: V2b neurons and cerebrospinal fluid-contacting Kolmer-Agduhr (KA) neurons (also called CSF-cNs). Our data provide the first demonstration, in any vertebrate, that Tal1 and Gata3 are required for correct development of KA and V2b neurons, respectively. We also uncover differences in the genetic regulation of V2b cell development in zebrafish compared to mouse. In addition, we demonstrate that Sox1a and Sox1b are expressed by KA and V2b neurons in zebrafish, which differs from mouse, where Sox1 is expressed by V2c neurons. KA neurons can be divided into ventral KA″ neurons and more dorsal KA′ neurons. Consistent with previous morpholino experiments, our mutant data suggest that Tal1 and Gata3 are required in KA′ but not KA″ cells, whereas Gata2a is required in KA″ but not KA′ cells, even though both of these cell types co-express all three of these transcription factors. In gata2a mutants, cells in the KA″ region of the spinal cord lose expression of most KA″ genes and there is an increase in the number of cells expressing V3 genes, suggesting that Gata2a is required to specify KA″ and repress V3 fates in cells that normally develop into KA″ neurons. On the other hand, our data suggest that Gata3 and Tal1 are both required for KA′ neurons to differentiate from progenitor cells. In the KA′ region of these mutants, cells no longer express KA′ markers and there is an increase in the number of mitotically-active cells. Finally, our data demonstrate that all three of these transcription factors are required for later stages of V2b neuron differentiation and that Gata2a and Tal1 have different functions in V2b development in zebrafish than in mouse.

In this protocol, we describe proximal ligation assay (PLA), an antibody-based detection method for protein-protein interaction. This method relies on specific binding of individual primary antibodies to the two putative interacting proteins. The primary antibodies need to have different hosts. The secondary antibodies against the two hosts have complementary oligonucleotide moieties attached to them. If the two antigens are in close proximity (presumably interacting with each other), the complementary oligonucleotides can anneal and fluorescent nucleotides can be incorporated in a single DNA polymerization step. Under a microscope, these reactions appear as punctate fluorescent spots, indicating successful PLA reaction and suggesting protein-protein interaction between the two antigens.

Mixed siliciclastic–carbonate rocks constitute the Upper Cretaceous Garuda-mangalam Sandstone Formation, Ariyalur (India), and offer an opportunity to look into the broad spectrum of mixing of compositionally and genetically different components. The palaeogeographic reconstruction indicates that deposition in the nearshore zone differed strongly in energy and active processes operatives due to the presence of a shore-parallel river-mouth bar. The western wing of the Mississippi bird-foot delta is considered to be a present-day analogon. Facies analysis in combination with petrography clearly shows the variability in palaeoenvironmental characteristics, both biogenic and non-biogenic. It also indicates diagenetic uptake of carbonate that filled empty spaces and actively replaced original components. Chemical staining followed by limited application of cathodoluminescence and energy dispersive X-ray analysis (EDAX) hint at intricacies in mixing arising from the compositional variations in the carbonate components. A model of siliciclastic–carbonate sediment mixing, including both the depositional and diagenetic developments, is presented; it is aimed at generating a better overview of, and a deeper insight into, the physical and chemical mechanisms involved.

A stretch of the modern hypersaline coastal plain of the Gulf of Cambay was chosen to examine the distribution of the microbial mat-related structures (MRS) on siliciclastic sediments in the intertidal and supratidal zones. The abundance of MRS increases from the lower intertidal zone to the upper supratidal zone while the type of MRS records a systematic change. While the lower intertidal zone exhibits wrinkle structures, sieve-like surfaces and patchy ripples in places, the upper intertidal zone exhibits diverse MRS related to reduced current activity on the mat layer and intermittent exposure. MRS in the upper intertidal zone include wrinkle structures, sieve-like surfaces, gas domes, reticulated surfaces, multi-directional ripples, patchy ripples, rolled-up mat fragments, setulfs and occasional petee ridges and cracked mat surfaces. The lower supratidal zone is characterized by increased occurrence of petee ridges, gas domes and cracked mat surfaces compared to the upper intertidal zone. The upper supratidal zone is distinguished by the presence of abundant cracked mat surfaces, petee ridges, gas domes and wrinkle structures. The presence of cm-scale, disc-shaped microbial colonies (DMC) with a variety of internal structures is a unique feature of the Gulf of Cambay study area. While wrinkle structures occur in all the coastal zones, setulfs occur close to the boundary between the upper intertidal and lower supratidal zones. An attempt has been made to compare the distribution of MRS in this modern environment with those in the ~1.6 Ga Chorhat Sandstone of the Vindhyan Supergroup for high-resolution palaeoenvironmental interpretation. The upper part of the intertidal segment of the Chorhat Sandstone is distinguished from its lower part by the presence of abundant cracked mat surfaces, petee ridges and gas domes in the former, while wrinkle structures, Kinneyia, rolled-up mat fragments, patchy ripples and multi-directional ripples are equally abundant in both parts. The lower part of the intertidal segment of the Chorhat Sandstone is thus analogous to the upper intertidal zone of the modern Gulf of Cambay environment, while the upper part of the Chorhat intertidal segment reflects prolonged exposure close to the high tide line. The bottom-most part of the intertidal segment of the Chorhat Sandstone with fewer MRS corresponds to the lower intertidal zone at Cambay. Inferred disc-shaped microbial fossils within Vindhyan sandstones are analogous to the DMC found in the modern environment and these features do not have any biostratigraphic implication.

The lignite deposits of Kutch, India are stratigraphically referred to the Naredi Formation and considered to be Early Eocene in age. The biostratigraphy of the older mine at Panandhro and a newly opened mine at Matanomadh has constrained the upper age limit of lignite to the early Bartonian. Its lower age may extend to the late Lutetian. Temporally the formation of lignite corresponds to the warming event of the Middle Eocene and suggests a humid climate at the onset of the warming. The previous palynological studies have already suggested dominance of tropical angiospermic pollen. A diverse assemblage of fossil whales and other vertebrates, many of them supposedly the oldest representatives, were reported from Panandhro mine. These were initially assigned to the Early Eocene and later to the Lute‑ tian age. The present biostratigraphic study revises their age to the Early Bartonian.

The microbiome is important in the evolution of the immune system in children; however, information is lacking regarding the composition of the pediatric ocular microbiome and its surrounding structures. A prospective, cross-sectional study of the ocular microbiome was conducted in children t-test, diversity indices, and principal coordinate analysis. A total of 15 children were enrolled. The ocular surface microbiome was predominantly composed of Proteobacteria, whereas Bacteroidetes dominated the eyelid margin, and Firmicutes dominated the periocular skin. Despite these variations, no statistically significant compositional differences were found with Bray-Curtis analysis. The conjunctiva had the lowest Shannon diversity index with a value of 2.3, which was significantly lower than those of the eyelid margin (3.4, p = 0.01) and the periocular skin (3.5, p = 0.001). However, the evenness of the species using Faith’s phylogenetic diversity index was similar at all sites. Overall, the ocular surface microbiome is dominated by Proteobacteria in children. The niche is similar to the surrounding structures in terms of composition, but has a lower number and relative abundance of species.

A combined micropalaeontological and sedimentological investigation of the Early Eocene Naredi Formation (thickness varying between 20 m and 60 m) reveals a complete third-order cycle and six fourth-order sea level cycles. Within the third-order cycle the foraminiferal abundance and diversity gradually increase upwards and reach their maximum values at about 41 m thickness above the base of the formation and subsequently decrease upward and finally give way upward to an unfossiliferous zone at the topmost part. Within a fourth-order cycle foraminiferal abundance and diversity exhibit a similar increasing and decreasing pattern. Bounded between two unconformities the Naredi Formation represents a sequence. A highly fossiliferous Assilina-bearing limestone interval represents the maximum flooding zone which separates the transgressive systems tract at the base from the highstand systems tract at the top.

Opiates are among the most prescribed drugs for pain management. However, morphine use or abuse results in significant gut bacterial translocation and predisposes patients to serious infections with gut origin. The mechanism underlying this defect is still unknown. In this report, we investigated the mechanisms underlying compromised gut immune function and bacterial translocation following morphine treatment. We demonstrate significant bacterial translocation to mesenteric lymph node (MLN) and liver following morphine treatment in wild-type (WT) animals that was dramatically and significantly attenuated in Toll-like receptor (TLR2 and 4) knockout mice. We further observed significant disruption of tight junction protein organization only in the ileum but not in the colon of morphine treated WT animals. Inhibition of myosin light chain kinase (MLCK) blocked the effects of both morphine and TLR ligands, suggesting the role of MLCK in tight junction modulation by TLR. This study conclusively demonstrates that morphine induced gut epithelial barrier dysfunction and subsequent bacteria translocation are mediated by TLR signaling and thus TLRs can be exploited as potential therapeutic targets for alleviating infections and even sepsis in morphine-using or abusing populations.

During vertebrate development, trunk neural crest cells delaminate along the entire length of the dorsal neural tube and initially migrate as a non-segmented sheet. As they enter the somites, neural crest cells rearrange into spatially restricted segmental streams. Extracellular matrix components are likely to play critical roles in this transition from a sheet-like to a stream-like mode of migration, yet the extracellular matrix components and their modifying enzymes critical for this transition are largely unknown. Here, we identified the glycosyltransferase Lh3, known to modify extracellular matrix components, and its presumptive substrate Collagen18A1, to provide extrinsic signals critical for neural crest cells to transition from a sheet-like migration behavior to migrating as a segmental stream. Using live cell imaging we show that in lh3 null mutants, neural crest cells fail to transition from a sheet to a stream, and that they consequently enter the somites as multiple streams, or stall shortly after entering the somites. Moreover, we demonstrate that transgenic expression of lh3 in a small subset of somitic cells adjacent to where neural crest cells switch from sheet to stream migration restores segmental neural crest cell migration. Finally, we show that knockdown of the presumptive Lh3 substrate Collagen18A1 recapitulates the neural crest cell migration defects observed in lh3 mutants, consistent with the notion that Lh3 exerts its effect on neural crest cell migration by regulating post-translational modifications of Collagen18A1. Together these data suggest that Lh3-Collagen18A1 dependent ECM modifications regulate the transition of trunk neural crest cells from a non-segmental sheet like migration mode to a segmental stream migration mode.