Stiffness of the human foot and evolution of the transverse arch.

The stiff human foot enables an efficient push-off when walking or running, and was critical for the evolution of bipedalism1-6. The uniquely arched morphology of the human midfoot is thought to stiffen it5-9, whereas other primates have flat feet that bend severely in the midfoot7,10,11. However, the relationship between midfoot geometry and stiffness remains debated in foot biomechanics12,13, podiatry14,15 and palaeontology4-6. These debates centre on the medial longitudinal arch5,6 and have not considered whether stiffness is affected by the second, transverse tarsal arch of the human foot16. Here we show that the transverse tarsal arch, acting through the inter-metatarsal tissues, is responsible for more than 40% of the longitudinal stiffness of the foot. The underlying principle resembles a floppy currency note that stiffens considerably when it curls transversally. We derive a dimensionless curvature parameter that governs the stiffness contribution of the transverse tarsal arch, demonstrate its predictive power using mechanical models of the foot and find its skeletal correlate in hominin feet. In the foot, the material properties of the inter-metatarsal tissues and the mobility of the metatarsals may additionally influence the longitudinal stiffness of the foot and thus the curvature-stiffness relationship of the transverse tarsal arch. By analysing fossils, we track the evolution of the curvature parameter among extinct hominins and show that a human-like transverse arch was a key step in the evolution of human bipedalism that predates the genus Homo by at least 1.5 million years. This renewed understanding of the foot may improve the clinical treatment of flatfoot disorders, the design of robotic feet and the study of foot function in locomotion.

Validation of the VirCapSeq-VERT system for differential diagnosis, detection, and surveillance of viral infections.

IMPORTANCE: Broad range assay for accurate and sensitive diagnostics.

Anatomical insights into fish terrestrial locomotion: A study of barred mudskipper (Periophthalmus argentilineatus) fins based on µCT 3D reconstructions.

Mudskippers are a group of extant ray-finned fishes with an amphibious lifestyle and serve as exemplars for understanding the evolution of amphibious capabilities in teleosts. A comprehensive anatomical profile of both the soft and hard tissues within their propulsive fins is essential for advancing our understanding of terrestrial locomotor adaptations in fish. Despite the ecological significance of mudskippers, detailed data on their musculoskeletal anatomy remains limited. In the present research, we utilized contrast-enhanced high-resolution microcomputed tomography (µCT) imaging to investigate the barred mudskipper, Periophthalmus argentilineatus. This technique enabled detailed reconstruction and quantification of the morphological details of the pectoral, pelvic, and caudal fins of this terrestrial mudskipper, facilitating comparison with its aquatic relatives. Our findings reveal that P. argentilineatus has undergone complex musculoskeletal adaptations for terrestrial movement, including an increase in muscle complexity and muscle volume, as well as the development of specialized structures like aponeuroses for pectoral fin extension. Skeletal modifications are also evident, with features such as a reinforced shoulder-pelvic joint and thickened fin rays. These evolutionary modifications suggest biomechanically advanced fins capable of overcoming the gravitational challenges of terrestrial habitats, indicating a strong selective advantage for these features in land-based environments. The unique musculoskeletal modifications in the fins of mudskippers like P. argentilineatus, compared with their aquatic counterparts, mark a critical evolutionary shift toward terrestrial adaptations. This study not only sheds light on the specific anatomical changes facilitating this transition but also offers broader insights into the early evolutionary mechanisms of terrestrial locomotion, potentially mirroring the transformative journey from aquatic to terrestrial life in the lineage leading to tetrapods.

Detection of Perfluorooctanoic and Perfluorodecanoic Acids on a Graphene-Based Electrochemical Sensor Aided by Computational Simulations.

Perfluoroalkyl carboxylic acids (PFCAs) exhibit high chemical and thermal stability, rendering them versatile for various applications. However, their notable toxicity poses environmental and human health concerns. Detecting trace amounts of these chemicals is crucial to mitigate risks. Electrochemical sensors surpass traditional methods in sensitivity, selectivity, and cost-effectiveness. In this study, a graphene nanosheet-based sensor was developed for detecting perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA). Using the Hummer method, graphene nanosheets were synthesized and characterized in terms of morphology, structural ordering, and surface topology. Ab initio molecular dynamics simulations determined the molecular interaction of per- and poly-fluoroalkyl substances (PFASs) with the sensor material. The sensor exhibited high sensitivity (50.75 µA·µM-1·cm-2 for PFOA and 29.58 µA·µM-1·cm-2 for PFDA) and low detection limits (10.4 nM for PFOA and 16.6 nM for PFDA) within the electrode dynamic linearity range of 0.05-500.0 µM (PFOA) and 0.08-500.0 µM (PFDA). Under optimal conditions, the sensor demonstrated excellent selectivity and recovery in testing for PFOA and PFDA in environmental samples, including spiked soil, water, spoiled vegetables, and fruit samples.

Strong and reliable synaptic communication between pyramidal neurons in adult human cerebral cortex.

Synaptic transmission constitutes the primary mode of communication between neurons. It is extensively studied in rodent but not human neocortex. We characterized synaptic transmission between pyramidal neurons in layers 2 and 3 using neurosurgically resected human middle temporal gyrus (MTG, Brodmann area 21), which is part of the distributed language circuitry. We find that local connectivity is comparable with mouse layer 2/3 connections in the anatomical homologue (temporal association area), but synaptic connections in human are 3-fold stronger and more reliable (0% vs 25% failure rates, respectively). We developed a theoretical approach to quantify properties of spinous synapses showing that synaptic conductance and voltage change in human dendritic spines are 3-4-folds larger compared with mouse, leading to significant NMDA receptor activation in human unitary connections. This model prediction was validated experimentally by showing that NMDA receptor activation increases the amplitude and prolongs decay of unitary excitatory postsynaptic potentials in human but not in mouse connections. Since NMDA-dependent recurrent excitation facilitates persistent activity (supporting working memory), our data uncovers cortical microcircuit properties in human that may contribute to language processing in MTG.

First report of Candidatus Phytoplasma australasia (16SrII- subgroup D) associated with virescence of Chia (Salvia hispanica L.) from India.

Chia (Salvia hispanica L., Lamiaceae) is an important commercial and medicinal crop recently popularized in India and widely cultivated in Karnataka (Joy et al., 2022). During the field survey of chia crop diseases, characteristic virescence like symptoms were observed at Main Agricultural Research Station, UAS, Raichur as well as at Mysuru and HD Kote region. The incidence was ranged from 2 - 4 per cent in an area of 30 hectares. Typical symptoms associated with chia are malformed shoot and/or inflorescence axis with reduced floral parts with greenish florets. The stem axis become thick, flattened, leaves are reduced towards terminal region. A total of five phytoplasma suspected samples and five suspected healthy samples were used for identification purpose. The Plant Genomic DNA Miniprep Kit (Sigma Aldrich, USA) was used to extract the DNA from five symptomatic and five asymptomatic samples and the DNA was used as template to amplify the phytoplasma-specific 16S rDNA gene using P1/P7 primers (Deng and Hiruki, 1991; Schneider et al., 1995) followed by nested PCR using R16F2n/R16R2 primers (Gundersen and Lee 1996). The expected 1.25-kb amplicon was detected from the suspected symptomatic samples. Nested PCR products were purified and sequenced from both the directions using ABIX370 Genetic Analyzer (Applied Biosystems, Waltham, MA). The analysis revealed that all five sequences shared 100 per cent identity with Candidatus Phytoplasma aurantifolia (OM649850, ON975012) and Tomato big bud phytoplasma (EF193359). The in-silico RFLP pattern of F2n/R2 primed region of 16S rDNA gene analyzed by using iPhyClassifier (Zhao et al. 2009) revealed that the sequence shared 98.72 per cent nucleotide sequence similarity with coefficient value of 1.00 to the reference strain RFLP pattern of 16Sr group II, subgroup D (witches'-broom disease of lime; U15442). Based on 16SrDNA sequences and in-silico RFLP analysis, the phytoplasma associated with the chia virescence was identified as a member of 16SrII-D group. Further, SecA gene was also amplified from the samples using SecAfor1/SecArev3 primer pair (Hodgetts et al., 2008). All samples produced ~400 bp products and sequenced as detailed above. Sequence analysis by nBLAST revealed 100 per cent similarity to Ca. P. australasia (MW020545) and Ca. P. aurantifolia isolate Idukki Kerala 1 (MK726369) both representing 16SrII-D group phytoplasma. The representative sequence (16Sr: PP359693, PP359694; secA:PP386558, PP386559) were deposited in GenBank. Chia virescence phytoplasma belonging to Ca. phytoplasma australasia has not been reported anywhere. The phytopathological studies associated with chia crop are very limited. Joy et al. (2022) reported the occurrence of foot rot disease caused by Athelia rolfsii. Several hosts are recorded to be associated with 16SrII D phytoplasma which includes china aster, eggplant and crotalaria (Mahadevakumar et al., 2017, Yadav et al., 2016a, b). Now the wide occurrence of the phytoplasma in the area might have transmitted by vectors. The occurrence of virescence is of great importance as it affects the overall yield which reduces the market value. To our knowledge, this is the first report of a group 16SrII-D phytoplasma associated with chia virescence in India.

Ligand Control in Co-Catalyzed Regio- and Enantioselective Hydroboration: Homoallyl Secondary Boronates via Uncommon 4,3-Hydroboration of 1,3-Dienes.

Enantiopure homoallylic boronate esters are versatile intermediates because the C-B bond in these compounds can be stereospecifically transformed into C-C, C-O, and C-N bonds. Regio- and enantioselective synthesis of these precursors from 1,3-dienes has few precedents in the literature. We have identified reaction conditions and ligands for the synthesis of nearly enantiopure (er >97:3 to >99:1) homoallylic boronate esters via a rarely seen cobalt-catalyzed [4,3]-hydroboration of 1,3-dienes. Monosubstituted or 2,4-disubstituted linear dienes undergo highly efficient regio- and enantioselective hydroboration with HBPin catalyzed by [(L*)Co]+[BARF]-, where L* is typically a chiral bis-phosphine ligand with a narrow bite angle. Several such ligands (e.g., i-PrDuPhos, QuinoxP*, Duanphos, and BenzP*) that give high enantioselectivities for the [4,3]-hydroboration product have been identified. In addition, the equally challenging problem of regioselectivity is uniquely solved with a dibenzooxaphosphole ligand, (R,R)-MeO-BIBOP. A cationic cobalt(I) complex of this ligand is a very efficient (TON >960) catalyst while also providing excellent regioselectivities (rr >98:2) and enantioselectivities (er >98:2) for a broad range of substrates. A detailed computational investigation of the reactions using Co complexes from two widely different ligands (BenzP* and MeO-BIBOP) employing the B3LYP-D3 density functional theory provides key insights into the mechanism and the origins of selectivities. The computational results are in full agreement with the experiments. For the complexes we have examined thus far, the relative stabilities of the diastereomeric diene-bound complexes [(L*)Co(η4-diene)]+ lead to the initial diastereofacial selectivity, which in turn is retained in the subsequent steps, providing exceptional enantioselectivity for the reactions.

Concurrent Hepatoblastoma and Wilms Tumor Leading to Diagnosis of Beckwith-Wiedemann Syndrome.

Beckwith-Wiedemann syndrome (BWS) is an epigenetic overgrowth disorder and cancer predisposition syndrome caused by imprinting defects of chromosome 11p15.5-11p15.4. BWS should be considered in children with atypical presentations of embryonal tumors regardless of clinical phenotype. Risk of malignancy correlates with specific molecular subgroups of BWS making molecular subclassification important for appropriate cancer screening. We report the first case of concurrent embryonal tumors in a phenotypically normal child, leading to the diagnosis of BWS with paternal uniparental disomy and describe the molecular classification of BWS as it relates to malignancy risk, along with approach to management.

Papillary Intralymphatic Angioendothelioma in a Child With PIK3CA-Related Overgrowth Spectrum: Implication of PI3K Pathway in the Vascular Tumorigenesis.

Papillary intralymphatic angioendothelioma (PILA) is an extremely rare vascular tumor and its pathogenesis is unknown. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-related overgrowth spectrum (PROS) is a heterogeneous group of disorders caused by mosaicism for activating mutations of PIK3CA and characterized by asymmetric overgrowth, skeletal anomalies, skin lesions, and vascular malformations. An association between PILA and PROS has not been known. We report a case of PILA involving the spleen of a young girl with the clinical and molecular diagnosis of PROS. Sequencing of the patient's germ-line DNA detected a pathogenic PIK3CA variant c.1357G>A in 10.6% of alleles. Splenectomy revealed a 4-cm tumor composed of ectatic lymphatics with intraluminal papillary projections, consistent with PILA. The tumor cells showed immunohistochemical expression of CD31, CD34, ERG, FLI-1, PROX1, and caldesmon, while D2-40 was negative. The latter may suggest that the tumor derived from an endothelial precursor arrested in the final steps of lymphothelial differentiation, in keeping with the known role of the PIK3CA-governed molecular pathway in the progression of vascular progenitors to mature endothelial cells. The data implicates PIK3CA in the pathogenesis of PILA and broadens the spectrum of phenotypic expressions of PROS.

Study of Efficacy of Injection Remdesivir in Patients of COVID-19.

INTRODUCTION: The coronavirus disease of 2019 (COVID-19) is a highly contagious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). World Health Organization (WHO) declared it a pandemic on 11th March 2020. Injectable remdesivir (RDV), a repurposed antiviral, was first accorded approval by the United States of America (USA) Food and Drug Administration (FDA) on 1st May 2020, for emergency use to treat suspected or laboratory-confirmed COVID-19 patients. Interim analysis of the Solidarity trial revealed no benefits in patients treated with RDV in any group of patients with COVID-19. Here, we have attempted to place our data on the efficacy of RDV in patients of COVID-19 with moderate to severe categories. MATERIALS AND METHODS: A retrospective review and data analysis of 100 COVID-19 patients with reverse transcriptase polymerase chain reaction (RT-PCR)/rapid antigen test positive was performed. Among them, 50 received RDV in addition to the standard treatment protocol (STP), while the remaining 50 received only the STP. STP is an injectable steroid and heparin, along with other supportive management. Prevalent government guidelines were followed as per usual for the classification of the patients and treatment protocol. Every day of hospitalization, the status of respiratory support was checked, and every 3rd-day inflammatory markers [C-reactive protein (CRP) and D-dimer] were measured until the patient was discharged or died. Statistical analysis of the data was done using online software. RESULTS: Age and comorbidity distribution in both groups ensures adequate matching between the two groups. A statistically significant difference in hospitalization days was obtained in RDV-treated patients (15 vs 19 days, p-value -0.003). Statistically significant differences were not found in mortality (6 vs 10 deaths, p-value -0.27) and reduction in oxygen (O2)/ventilatory support requirements (p-value -0.75) in the RDV group as compared to other groups. The difference in the value of CRP (p-value 0.001) and D-dimer (p-value 0.049) on day 5 is statistically significant in the RDV group as compared to the other groups. DISCUSSION: The finding of a reduction in days of hospitalization was similar to the Adaptive COVID-19 Treatment Trial (ACTT) 1 study conducted by Beigel et al. The mortality data were also comparable to those from WHO's Solidarity trial. No similarity was found in data on the reduction in ordinal scale from higher to lower scale for O2/ventilatory support on day 10 from 0. Similarity regarding the reduction in values of inflammatory markers on day 5 was found in studies conducted by Kannan et al. and Stoeckle et al. CONCLUSION: We found mortality benefit and reduction in O2 requirements/ventilatory support in RDV plus STP-administered cases as compared to STP only, but statistically, this difference is not significant, which suggests that mortality benefit in the RDV group in our study is merely by chance. Here, we can definitely conclude that days of hospital stay and inflammatory markers are reduced in the RDV plus STP-administered group, and the difference between the two groups is statistically significant, which suggests that early use of RDV could shorten the time to clinical improvement.

Scientific characterization methods for better utilization of cattle dung and urine: a concise review.

Cattle are usually raised for food, manure, leather, therapeutic, and draught purposes. Biowastes from cattle, such as dung and urine, harbor a diverse group of crucial compounds, metabolites/chemicals, and microorganisms that may benefit humans for agriculture, nutrition, therapeutics, industrial, and other utility products. Several bioactive compounds have been identified in cattle dung and urine, which possess unique properties and may vary based on agro-climatic zones and feeding practices. Therefore, cattle dung and urine have great significance, and a balanced nutritional diet may be a key to improved quality of these products/by-products. This review primarily focuses on the scientific aspects of biochemical and microbial characterization of cattle biowastes. Various methods including genomics for analyzing cattle dung and gas chromatography-mass spectroscopy for cattle urine have been reviewed. The presented information might open doors for the further characterization of cattle resources for heterogeneous applications in the production of utility items and addressing research gaps. Methods for cattle's dung and urine characterization.

A New Paradigm in Enantioselective Cobalt Catalysis: Cationic Cobalt(I) Catalysts for Heterodimerization, Cycloaddition, and Hydrofunctionalization Reactions of Olefins.

One of the major challenges facing organic synthesis in the 21st century is the utilization of abundantly available feedstock chemicals for fine chemical synthesis. Regio- and enantioselective union of easily accessible 1,3-dienes and other feedstocks like ethylene, alkyl acrylates, and aldehydes can provide valuable building blocks adorned with latent functionalities for further synthetic elaboration. Through an approach that relies on mechanistic insights and systematic examination of ligand and counterion effects, we developed an efficient cobalt-based catalytic system [(P∼P)CoX2/Me3Al] (P∼P = bisphosphine) to effect the first enantioselective heterodimerization of several types of 1,3-dienes with ethylene. In addition to simple cyclic and acyclic dienes, siloxy-1,3-dienes participate in this reaction, giving highly functionalized, nearly enantiopure silyl enolates, which can be used for subsequent C-C and C-X bond-forming reactions. As our understanding of the mechanism of this reaction improved, our attention was drawn to more challenging partners like alkyl acrylates (one of the largest volume feedstocks) as the olefin partners instead of ethylene. Prompted by the intrinsic limitations of using aluminum alkyls as the activators for this reaction, we explored the fundamental chemistry of the lesser known (P∼P)Co(I)X species and discovered that in the presence of halide sequestering agents, such as sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaBARF) or (C6F5)3B, certain chiral bisphosphine complexes are superb catalysts for regio- and enantioselective heterodimerization of 1,3-dienes and alkyl acrylates. We have since found that these cationic Co(I) catalysts, most conveniently prepared in situ by reduction of the corresponding cobalt(II) halide complexes by zinc in the presence of NaBARF, promote enantioselective [2 + 2]-cycloaddition between alkynes and an astonishing variety of alkenyl derivatives to give highly functionalized cyclobutenes. In reactions between 1,3-enynes and ethylene, the [2 + 2]-cycloaddition between the alkyne and ethylene is followed by a 1,4-addition of ethylene in a tandem fashion to give nearly enantiopure cyclobutanes with an all-carbon quaternary center, giving a set of molecules that maps well into many medicinally relevant compounds. In another application, we find that the cationic Co(I)-catalysts promote highly selective hydroacylation and 1,2-hydroboration of prochiral 1,3-dienes. Further, we find that a cationic Co(I)-catalyst promotes cycloisomerization followed by hydroalkenylation of 1,6-enynes to produce highly functionalized carbo- and heterocyclic compounds. Surprisingly the regioselectivity of the alkene addition depends on whether it is a simple alkene or an acrylate, and the acrylate addition produces an uncommon Z-adduct. This Account will provide a summary of the enabling basic discoveries and the attendant developments that led to the unique cationic Co(I)-complexes as catalysts for disparate C-C and C-B bond-forming reactions. It is our hope that this Account will stimulate further work with these highly versatile catalysts which are derived from an earth-abundant metal.

Phenogenomic heterogeneity of post-transplant plasmablastic lymphomas.

Plasmablastic lymphoma (PBL) is a rare and clinically aggressive neoplasm that typically occurs in immunocompromised individuals, including those with HIV infection and solid organ allograft recipients. Most prior studies have focused on delineating the clinicopathologic features and genetic attributes of HIV-related PBLs, where MYC deregulation and EBV infection, and more recently, mutations in JAK/STAT, MAP kinase, and NOTCH pathway genes have been implicated in disease pathogenesis. The phenotypic spectrum of post-transplant (PT)-PBLs is not well characterized and data on underlying genetic alterations are limited. Hence, we performed comprehensive histopathologic and immunophenotypic evaluation and targeted sequencing of 18 samples from 11 patients (8 males, 3 females, age range 12-76 years) with PT-PBL; 8 de novo and 3 preceded by other types of PTLDs. PT-PBLs displayed morphologic and immunophenotypic heterogeneity and some features overlapped those of plasmablastic myeloma. Six (55%) cases were EBV+ and 5 (45%) showed MYC rearrangement by fluorescence in situ hybridization. Recurrent mutations in epigenetic regulators (KMT2/MLL family, TET2) and DNA damage repair and response (TP53, mismatch repair genes, FANCA, ATRX), MAP kinase (KRAS, NRAS, HRAS, BRAF), JAK/STAT (STAT3, STAT6, SOCS1), NOTCH (NOTCH1, NOTCH3, SPEN), and immune surveillance (FAS, CD58) pathway genes were observed, with EBV+ and EBV- cases exhibiting similarities and differences in their mutational profiles. Clinical outcomes also varied, with survival ranging from 0-15.9 years postdiagnosis. Besides uncovering the biological heterogeneity of PT-PBL, our study highlights similarities and distinctions between PT-PBLs and PBLs occurring in other settings and reveals potentially targetable oncogenic pathways in disease subsets.

Pathological findings in COVID-19: A conventional autopsy-based study from India.

Background & objectives: Autopsy study has been considered the gold standard method for studying the effects of any disease on the body. Since COVID-19 is a novel disease, autopsy is crucial to understand its pathophysiology. This study was conducted to analyze the microscopic and macroscopic findings of various organs in COVID-19 and to associate those findings with clinical observations and laboratory findings. Methods: Conventional invasive autopsies were performed on 33 patients with COVID-19 from September 7, 2020 to December 23, 2020. All the organs were removed by routine dissection techniques and preserved in 10 per cent formalin. The tissues were processed and stained according to standard practices using haematoxylin-eosin (H & E) and periodic acid-schiff (PAS) stain. Results: The study included 28 males and 5 females with a median age of 61 yr (range 30-90 yr). Massive pulmonary oedema and thrombi in the lungs were the characteristic features macroscopically. On microscopic examination, diffuse alveolar damage in the exudative/proliferative phase was found in 29 (87.88%) cases. Among the other notable microscopic findings were bronchopneumonia and lung abscesses due to secondary bacterial infection (n=17, 51.52%), acute tubular injury (n=21, 63.64%) and thrombi in the lungs, heart, and kidneys. Interpretation & conclusions: COVID-19 primarily affected the respiratory and the renal systems in the vast majority of severely affected patients in our study. We also found signs of hypercoagulability, as evidenced by widespread thrombi in multiple organs, along with a raised d-dimer level and a hyperinflammatory state manifested by elevated inflammatory markers. Our autopsy findings and altered laboratory investigations support the role of immune-mediated cellular injury along with direct virus-mediated cellular damage.

First report of Athelia rolfsii (=Sclerotium rolfsii) associated with foot rot disease of Chrysanthemum morifolium in India.

Chrysanthemum morifolium L. is an important flower crop grown in different parts of Karnataka for its striking cut flowers and international market value. During a field survey (Mysore district, Karnataka, February, 2022), chrysanthemum fields were found infected with foot rot disease. The presence of white mycelial structures with sclerotia were recorded near the stem-soil interface. The disease incidence ranged 10-12% measured in an area of approximately 10 hectares. The infected plants showed quick wilt, yellowing and toppling of the entire plant. Infected plants from Doddamaragowdanahally and Rayanahally (n=15) were collected and associated fungal pathogen isolated after surface sterilization with NaOCl (1%) on potato dextrose agar (PDA) amended with chloramphenicol (50 mg/L). Fungal mycelia developed from the infected tissues were inoculated on to fresh PDA plates to obtained pure cultures for further identification. Fungal colonies with dense, aerial whitish-cottony mycelia with uniformly globoid sclerotia (0.284.2 mm) were observed after 15 days of incubation (28 ± 2°C). Sclerotia were white in the beginning and turned brown at maturity. The average number of sclerotia produced per plate ranged from 240 to >480 (n = 10). To further to confirm the identity of the isolates, two representative isolates (CmSr1 and CmSr2) was subjected to molecular identification based on ITS-rDNA sequences. Briefly, genomic DNA was isolated from 12 day old cultures using the CTAB method and ITS-rDNA was amplified using ITS1-ITS4 primers (White et al., 1990). An expected amplicon of >650 bp (ITS) was obtained and later sequenced from both the directions. The consensus sequences were analysed through nBLAST search which revealed that 100% sequence similarity with reference sequences of Athelia rolfsii (S. rolfsii) from GenBank database (MT127465, MN974137, KC292637; identity 656/656; 0 gaps). A phylogenetic tree obtained by the neighbor-joining method using MEGAX shared a common clade with the reference sequences retrieved and computed, thus confirming the identification based on sequence analysis and molecular phylogeny. The representative sequence of A. rolfsii isolates CmSr1 and CmSr2 isolates deposited in GenBank with Accession nos. ON456153 and ON456154, respectively. Based on etiology, morphological, cultural and molecular data the pathogen was identified as Athelia rolfsii (Curzi) Tu & Kimbrough (Syn: Sclerotium rolfsii Sacc.) (Mordue, 1974; Mahadevakumar et al., 2016, 2018). Plants (n=60) were inoculated with sclerotial bodies (2 sclerotia/plant) near stem soil interface under green house and covered with polythene bags (at 27 ± 2°C and 80% RH). Non-inoculated plants (n=20) served as controls. The development of foot rot disease was observed eight days after inoculation. A total of 48 plants showed the foot rot symptoms and 12 inoculated plants and control plants remained healthy. The identity of the fungus was confirmed by morphological and cultural characters after re-isolation. C. morifolium is an important flower crop in Karnataka. S. rolfsii is known to be associated with blight and collar rot of Chrysanthemum spp. from Kerala (Beena et al., 2002) but no species (host) identity provided. Therefore, to the best of our knowledge, this is the first report of foot rot disease caused by Athelia rolfsii on C. morifolium in India. Early diagnosis of this disease will help the farmers to adopt suitable management practices to avoid loss.

α- and ß-Functionalized Ketones from 1,3-Dienes and Aldehydes: Control of Regio- and Enantioselectivity in Hydroacylation of 1,3-Dienes.

Ketones are among the most widely used intermediates in organic synthesis, and their synthesis from inexpensive feedstocks could be quite impactful. Regio- and enantioselective hydroacylation reactions of dienes provide facile entry into useful ketone-bearing chiral motifs with an additional latent functionality (alkene) suitable for further elaboration. Three classes of dienes, 2- or 4-monosubstituted and 2,4-disubstituted 1,3-dienes, undergo cobalt(I)-catalyzed regio- and enantioselective hydroacylation, giving products with high enantiomeric ratios (er). These reactions are highly dependent on the ligands, and we have identified the most useful ligands and reaction conditions for each class of dienes. 2-Substituted and 2,4-disubstituted dienes predominantly undergo 1,2-addition, whereas 4-substituted terminal dienes give highly enantioselective 4,1- or 4,3-hydroacylation depending on the aldehyde, aliphatic aldehydes giving 4,1-addition and aromatic aldehydes giving 4,3-addition. Included among the substrates are feedstock dienes, isoprene (US$1.4/kg) and myrcene (US$129/kg), and several common aldehydes. We propose an oxidative dimerization mechanism that involves a Co(I)/Co(III) redox cycle that appears to be initiated by a cationic Co(I) intermediate. Studies of reactions using isolated neutral and cationic Co(I) complexes confirm the critical role of the cationic intermediates in these reactions. Enantioselective 1,2-hydroacylation of 2-trimethylsiloxy-1,3-diene reveals a hitherto undisclosed route to chiral siloxy-protected aldols. Finally, facile syntheses of the anti-inflammatory drug (S)-Flobufen (2 steps, 92% yield, >99:1 er) and the food additive (S)-Dihydrotagetone (1 step, 83% yield; 96:4 er) from isoprene illustrate the power of this method for the preparation of commercially relevant compounds.

The Many Faces of Pediatric Chronic Recurrent Multifocal Osteomyelitis (CRMO): A Practical Location- and Case-Based Approach to Differentiate CRMO From Its Mimics.

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disease of childhood and adolescence characterized by episodic bone pain. Diagnosis relies heavily on whole-body MRI and is made by excluding a wide variety of other disorders with overlapping imaging features, depending on location, marrow distribution, and the presence or absence of multifocality. We present an overview of the clinical and imaging features of CRMO and, through various clinical scenarios, provide tips for tailoring the differential diagnosis based on location and distribution of encountered abnormalities. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 3.

Formal Synthesis of (-)-Quinagolide: Diastereoselective Ring Expansion via a Bicyclic Aziridinium Ion Strategy to Access the Octahydrobenzo[g]quinoline Architecture.

The diastereoselective formal synthesis of (-)-quinagolide, a D2 receptor agonist, has been achieved. The synthesis started from l-pyroglutamic acid and relied on utilization of (a) a stereospecific catalytic hydrogenation and diastereoselective Horner-Emmons-Michael cascade to obtain functionalized prolinate, (b) a Lewis acid mediated Pummerer cyclization to construct a tricyclic fused ring system, and (c) a diastereoselective ring expansion via a bicyclic aziridinium intermediate to access the required 3-substituted piperidine scaffold.

Cytogenetic analysis of 130 renal oncocytomas identify three distinct and mutually exclusive diagnostic classes of chromosome aberrations.

The cytogenetic alterations in renal oncocytoma (RO) are poorly understood. We analyzed 130 consecutive RO for karyotypic alterations. Clonal chromosome abnormalities were identified in 63 (49%) cases, which could be categorized into three classes of mutually exclusive cytogenetic categories. Class 1 (N = 20) RO had diploid karyotypes with characteristic 11q13 rearrangement in balanced translocations with 10 or more different chromosome partners in all cases. We identified recurrent translocation partners at 5q35, 6p21, 9p24, 11p13-14, and 11q23, and confirmed that CCND1 gene rearrangement at 11q13 utilizing fluorescence in situ hybridization (FISH). Class 2 RO (N = 25) exhibited hypodiploid karyotypes with loss of chromosome 1 and/or losses of Y in males and X in females in all cases. The class 3 tumors comprising of 18 cases showed diverse types of abnormalities with the involvement of two or more chromosomes exclusive of abnormalities seen in classes 1 and 2 tumors. Furthermore, karyotypically uninformative cases were subjected to FISH analysis to identify classes 1 and 2 abnormalities. In this group, we found similar frequencies of CCND1 rearrangement, loss of chromosome 1 or Y as with karyotypically abnormal cases. We validated our results against 91 tumors from the Mitelman database. Correlation of clinical data with all the three classes of ROs showed no clear evidence of overall patient survival. Our findings support the hypothesis that RO exhibit three principal cytogenetic categories, which may have different roles in initiation and/or progression. These cytogenetic markers provide a key tool in the diagnostic evaluation of RO.

Genetic and phenotypic characterization of indolent T-cell lymphoproliferative disorders of the gastrointestinal tract.

Indolent T-cell lymphoproliferative disorders of the gastrointestinal tract are rare clonal T-cell diseases that more commonly occur in the intestines and have a protracted clinical course. Different immunophenotypic subsets have been described, but the molecular pathogenesis and cell of origin of these lymphocytic proliferations is poorly understood. Hence, we performed targeted next-generation sequencing and comprehensive immunophenotypic analysis of ten indolent T-cell lymphoproliferative disorders of the gastrointestinal tract, which comprised CD4+ (n=4), CD8+ (n=4), CD4+/CD8+ (n=1) and CD4-/CD8- (n=1) cases. Genetic alterations, including recurrent mutations and novel rearrangements, were identified in 8/10 (80%) of these lymphoproliferative disorders. The CD4+, CD4+/CD8+, and CD4-/CD8- cases harbored frequent alterations of JAK-STAT pathway genes (5/6, 82%); STAT3 mutations (n=3), SOCS1 deletion (n=1) and STAT3-JAK2 rearrangement (n=1), and 4/6 (67%) had concomitant mutations in epigenetic modifier genes (TET2, DNMT3A, KMT2D). Conversely, 2/4 (50%) of the CD8+ cases exhibited structural alterations involving the 3' untranslated region of the IL2 gene. Longitudinal genetic analysis revealed stable mutational profiles in 4/5 (80%) cases and acquisition of mutations in one case was a harbinger of disease transformation. The CD4+ and CD4+/CD8+ lymphoproliferative disorders displayed heterogeneous Th1 (T-bet+), Th2 (GATA3+) or hybrid Th1/Th2 (T-bet+/GATA3+) profiles, while the majority of CD8+ disorders and the CD4-/CD8- disease showed a type-2 polarized (GATA3+) effector T-cell (Tc2) phenotype. Additionally, CD103 expression was noted in 2/4 CD8+ cases. Our findings provide insights into the pathogenetic bases of indolent T-cell lymphoproliferative disorders of the gastrointestinal tract and confirm the heterogeneous nature of these diseases. Detection of shared and distinct genetic alterations of the JAK-STAT pathway in certain immunophenotypic subsets warrants further mechanistic studies to determine whether therapeutic targeting of this signaling cascade is efficacious for a proportion of patients with these recalcitrant diseases.