Global perspective of municipal solid waste and landfill leachate: generation, composition, eco-toxicity, and sustainable management strategies.

Globally, more than 2 billion tonnes of municipal solid waste (MSW) are generated each year, with that amount anticipated to reach around 3.5 billion tonnes by 2050. On a worldwide scale, food and green waste contribute the major proportion of MSW, which accounts for 44% of global waste, followed by recycling waste (38%), which includes plastic, glass, cardboard, and paper, and 18% of other materials. Population growth, urbanization, and industrial expansion are the principal drivers of the ever-increasing production of MSW across the world. Among the different practices employed for the management of waste, landfill disposal has been the most popular and easiest method across the world. Waste management practices differ significantly depending on the income level. In high-income nations, only 2% of waste is dumped, whereas in low-income nations, approximately 93% of waste is burned or dumped. However, the unscientific disposal of waste in landfills causes the generation of gases, heat, and leachate and results in a variety of ecotoxicological problems, including global warming, water pollution, fire hazards, and health effects that are hazardous to both the environment and public health. Therefore, sustainable management of MSW and landfill leachate is critical, necessitating the use of more advanced techniques to lessen waste production and maximize recycling to assure environmental sustainability. The present review provides an updated overview of the global perspective of municipal waste generation, composition, landfill heat and leachate formation, and ecotoxicological effects, and also discusses integrated-waste management approaches for the sustainable management of municipal waste and landfill leachate.

On Application of Lightweight Models for Rice Variety Classification and Their Potential in Edge Computing.

Rice is one of the fundamental food items that comes in many varieties with their associated benefits. It can be sub-categorized based on its visual features like texture, color, and shape. Using these features, the automatic classification of rice varieties has been studied using various machine learning approaches for marketing and industrial use. Due to the outstanding performance of deep learning, several models have been proposed to assist in vision tasks like classification and detection. Regardless of their best results on accuracy metrics, they have been observed as overly excessive for computational resources and expert supervision. To address these challenges, this paper proposes three deep learning models that offer similar performance with 10% lighter computational overhead in comparison to existing best models. Moreover, they have been trained for end-to-end flow to demonstrate minimum expert supervision for pre-processing and feature engineering sub-tasks. The results can be observed as promising for classifying rice among five varieties, namely Arborio, Basmati, Ipsala, Jasmine, and Karacadag. The process and performance of the trained models can be extended for edge and mobile devices for field-specific tasks autonomously.

Transition metal doped CeO2 for photocatalytic removal of 2-chlorophenol in the exposure of indoor white light and antifungal activity.

Besides natural sunlight and expensive artificial lights, economical indoor white light can play a significant role in activating a catalyst for photocatalytic removal of organic toxins from contaminated water. In the current effort, CeO2 has been modified with Ni, Cu, and Fe through doping methodology to study the removal of 2-chlorophenol (2-CP) in the illumination of 70 W indoor LED white light. The absence of additional diffractions due to the dopants and few changes such as reduction in peaks' height, minor peak shift at 2θ (28.525°) and peaks' broadening in XRD patterns of modified CeO2 verifies the successful doping of CeO2. The solid-state absorption spectra revealed higher absorbance of Cu-doped CeO2 whereas a lower absorption response was observed for Ni-doped CeO2. An interesting observation regarding the lowering of indirect bandgap energy of Fe-doped CeO2 (∼2.7 eV) and an increase in Ni-doped CeO2 (∼3.0 eV) in comparison to pristine CeO2 (∼2.9 eV) was noticed. The process of e -- h + recombination in the synthesized photocatalysts was also investigated through photoluminescence spectroscopy. The photocatalytic studies revealed the greater photocatalytic activity of Fe-doped CeO2 with a higher rate (∼3.9 × 10-3 min-1) among all other materials. Moreover, kinetic studies also revealed the validation of the Langmuir-Hinshelwood kinetic model (R2 = 0.9839) while removing 2-CP in the exposure of indoor light with a Fe-doped CeO2 photocatalyst. The XPS analysis revealed the existence of Fe3+, Cu2+ and Ni2+ core levels in doped CeO2. Using the agar well-diffusion method, the antifungal activity was assessed against the fungus M. fructicola and F. oxysporum. Compared to CeO2, Ni-doped CeO2, and Cu-doped CeO2 nanoparticles, the Fe-doped CeO2 nanoparticles have outstanding antifungal properties.

MTORC2 is a physiological hydrophobic motif kinase of S6 Kinase 1.

Ribosomal protein S6 kinase 1 (S6K1), a major downstream effector molecule of mTORC1, regulates cell growth and proliferation by modulating protein translation and ribosome biogenesis. We have recently identified eIF4E as an intermediate in transducing signals from mTORC1 to S6K1 and further demonstrated that the role of mTORC1 is restricted to inducing eIF4E phosphorylation and interaction with S6K1. This interaction relieves S6K1 auto-inhibition and facilitates its hydrophobic motif (HM) phosphorylation and activation as a consequence. These observations underscore a possible involvement of mTORC1 independent kinase in mediating HM phosphorylation. Here, we report mTORC2 as an in-vivo/physiological HM kinase of S6K1. We show that rapamycin-resistant S6K1 truncation mutant ∆NH∆CT continues to display HM phosphorylation with selective sensitivity toward Torin-1. We also show that HM phosphorylation of wildtype S6K1and ∆NH∆CT depends on the presence of mTORC2 regulatory subunit-rictor. Furthermore, truncation mutagenesis and molecular docking analysis reveal the involvement of a conserved 19 amino acid stretch of S6K1 in mediating interaction with rictor. We finally show that deletion of the 19 amino acid region from wildtype S6K1 results in loss of interaction with rictor, with a resultant loss of HM phosphorylation regardless of the presence of functional TOS motif. Our data demonstrate that mTORC2 acts as a physiological HM kinase that can activate S6K1 after its auto-inhibition is overcome by mTORC1. We, therefore, propose a novel mechanism for S6K1 regulation where mTOR complexes 1 and 2 act in tandem to activate the enzyme.

Temporal trends in the cost and use of first-line treatments for infantile epileptic spasms syndrome.

OBJECTIVE: To describe the temporal trends in the cost and use of adrenocorticotropic hormone (ACTH), oral prednisolone, and vigabatrin, the first-line treatments for infantile epileptic spasms syndrome (IESS). METHODS: Retrospective observational study using the MarketScan Commercial database from 2006 to 2020. We identified patients with IESS diagnosed between birth and 18 months of age who received at least one of the first-line treatments within 60 days of diagnosis. Costs were adjusted for inflation using the Gross Domestic Product Implicit Price Deflator. RESULTS: A total of 1131 patients received at least one first-line treatment (median [p25 -p75 ] age: 6.3 [4.5-8.3] months, 55% male), of whom 592 patients received ACTH, 363 patients received oral prednisolone, and 355 patients received vigabatrin. After adjusting for inflation, the median average wholesale price of a 14-day course of treatment increased for ACTH from $3718 in 2006 to $100 457 in 2020, ~2700% (by a factor of 27), whereas it decreased for oral prednisolone from $169 in 2006 to $89 in 2020, ~50% (by a factor of 0.5), and increased for vigabatrin from $1206 in 2009 (first year with data on vigabatrin used for IESS) to $4102 in 2020, ~340% (by a factor of 3.4). During the first 60 days after diagnosis, inpatient admission days and costs where higher for ACTH than for oral prednisolone and vigabatrin-5.0 (3.0-8.3) days vs 2.0 (0.0-5.0) days vs 2.0 (0.0-6.0) days, p < .0001; and $32 828 ($14 711-$67 216) vs $16 227 ($0-$35 829) vs $17 844 ($0-$47 642), p < .0001. ACTH use decreased from representing 78% of first-line treatments in 2006 to 18% in 2020 (p < .0001). Sensitivity analyses confirmed the robustness of the results. SIGNIFICANCE: The gap between the cost of ACTH and the cost of oral prednisolone or vigabatrin has widened markedly from 2006 to 2020, whereas the relative proportion of ACTH use has decreased.

Synthesis and Micromechanistic Studies of Sensitized Bentonite for Methyl Orange and Rhodamine-B Adsorption from Wastewater: Experimental and DFT-Based Analysis.

This work reports the formation of a novel adsorbent, prepared by activating bentonite with cinnamic acid, which is highly efficient to remove dyes from wastewater. The adsorption efficiency of the cinnamic acid activated bentonite was compared with unmodified bentonite by removing methyl orange and rhodamine-B from polluted water. The characterization was performed through X-ray diffraction (XRD) Fourier transform infrared (FTIR) and scanning electron microscopy (SEM). The results indicated that acidic pH and low temperature were more suitable for the selected dyes adsorption. The analysis of the data was done by the Langmuir and Freundlich isotherms; the Freundlich isotherm showed more suitability for the equilibrium data. The data were further analyzed by pseudo-first and pseudo-second-order models to study adsorption kinetics. The results showed that methyl orange and rhodamine-B adsorption obeyed pseudo-order kinetics. The results obtained from this research suggested that acid activation of bentonite with cinnamic acid increased the surface area of the clay and hence enhanced its adsorption efficiency. The maximum adsorption efficiency for the removal of methyl orange and rhodamine-B was up to 99.3 mg g-1 and 44.7 mg g-1, respectively, at 25 °C. This research provides an economical modification technique of bentonite, which makes it cost-effective and a good adsorbent for wastewater treatment.

Expanding the view of the molecular mechanisms of autophagy pathway.

Autophagy is an evolutionarily conserved multistep degradation mechanism in eukaryotes, that maintains cellular homoeostasis by replenishing cells with nutrients through catabolic lysis of the cytoplasmic components. This critically coordinated pathway involves sequential processing events that begin with initiation, nucleation, and elongation of phagophores, followed by the formation of  double-membrane vesicles known as autophagosomes. Finally, autophagosomes migrate towards and fuse with lysosomes in mammals and vacuoles in yeast and plants, for the eventual degradation of the intravesicular cargo. Here, we review the recent advances in our understanding of the molecular events that define the process of autophagy.

Deciphering waste bound nitrogen by employing psychrophillic Aporrectodea caliginosa and priming of coprolites by associated heterotrophic nitrifiers under high altitude Himalayas.

Himalayan ecosystem is characterized by its fragile climate with rich repositories of biodiversity. Waste collection and disposal are becoming increasingly difficult due to topographical variations. Aporrectodea caligenosa, a versatile psychrophillic soil dweller, is a useful biocatalyst with potent bio-augmented capability for waste treatment at low temperatures. Microcosm experiments were conducted to elucidate the comprehensive nature of biogenic nitrogen transformation to NH4+ and NO3- produced by coupling of earthworm-microbes. Higher biogenic recovery of NH4+-N from coprolites of garden soil (47.73 ± 1.16%) and Himalayan goat manure (86.32 ± 0.92%) with an increment of 14.12 and 47.21% respectively over their respective control (without earthworms) with a linear decline beyond 4th week of incubation was reported. NO3--N recovery progressively sustained in garden soil and goat manure coprolites during entire incubation with highest 81.81 ± 0.45 and 87.20 ± 1.08 µg-N g-1dry weight recorded in 6th and 5th week of incubation respectively and peak increments as 38.58 and 53.71% relative to respective control (without earthworms). Declined NH4+-N in coprolites at low temperature (15.0 ± 2.0 °C) evidenced increased nitrification rates by taking over the process by abundant nitrifying microbes. Steady de-nitrification with progressive incubation on an average was 16.95 ± 0.46 ng-N g-1 per week and 21.08 ± 0.87 ng-N g-1 per week compared to 14.03 ± 0.58 ng-N g-1 per week and 4.50 ± 0.31 ng-N g-1 per week in respective control treatments. Simultaneous heterotrophic nitrification and aerobic denitrification (SHNAD) was found to be a prominent bioprocess at low temperature that resulted in high and stable total nitrogen and nitrate accumulation from garden soil and goat manure with relative recovery efficiency of 11.12%, 14.97% and 14.20%; 19.34%. A. caligenosa shows promising prospects for mass applicability in biogenic N removal from manure of Himalayan goat.

A Phase Ib/II Randomized Study of RO4929097, a Gamma-Secretase or Notch Inhibitor with or without Vismodegib, a Hedgehog Inhibitor, in Advanced Sarcoma.

PURPOSE: Because the Hedgehog and Notch pathways are often overexpressed in mesenchymal malignancies, we evaluated the efficacy of concurrent inhibition of Notch and Hedgehog signaling using the gamma-secretase inhibitor (GSI) RO4929097 and the smoothened antagonist vismodegib in unresectable or metastatic sarcoma. PATIENTS AND METHODS: In this investigator-initiated trial, phase Ib used standard 3+3 dose escalation in which patients first received vismodegib once daily for 21 days, followed by the combination of RO4929097 concurrently with vismodegib in 21-day cycles. In phase II, patients were randomized to RO4929097 alone or in combination with vismodegib. RESULTS: Nine patients were treated in phase Ib with no dose-limiting toxicities. RO4929097 at 15 mg daily in combination with 150 mg daily of vismodegib was declared the recommended phase II dose. Most adverse events were grade ≤ 2. In phase II (closed early due to discontinuation of RO4929097 evaluation), 34 patients were randomized to RO4929097 alone and 33 to RO4929097 plus vismodegib. RO4929097 did not interfere with the steady-state concentration of vismodegib, while vismodegib reduced the plasma concentration of RO492909. No patients had an objective response. Neither progression-free nor overall survival differed significantly between treatment arms. Paired tumor biopsies from a subset of patients demonstrated inhibition of cleaved Notch. CONCLUSIONS: The combination of RO4929097 plus vismodegib was generally well tolerated. Although accrual to this study was not completed, vismodegib did not meaningfully enhance the clinical efficacy of RO4929097 in an unplanned analysis. GSIs and GSIs plus vismodegib can inhibit intratumoral Notch and downstream phosphorylated Akt signaling.

Psychrotolerant Mesorhizobium sp. Isolated from Temperate and Cold Desert Regions Solubilizes Potassium and Produces Multiple Plant Growth Promoting Metabolites.

Soil potassium (K) supplement depends intensively on the application of chemical fertilizers, which have substantial harmful environmental effects. However, some bacteria can act as inoculants by converting unavailable and insoluble K forms into plant-accessible forms. Such bacteria are an eco-friendly approach for enhancing plant K absorption and consequently reducing utilization of chemical fertilization. Therefore, the present research was undertaken to isolate, screen, and characterize the K solubilizing bacteria (KSB) from the rhizosphere soils of northern India. Overall, 110 strains were isolated, but only 13 isolates showed significant K solubilizing ability by forming a halo zone on solid media. They were further screened for K solubilizing activity at 0 °C, 1 °C, 3 °C, 5 °C, 7 °C, 15 °C, and 20 °C for 5, 10, and 20 days. All the bacterial isolates showed mineral K solubilization activity at these different temperatures. However, the content of K solubilization increased with the upsurge in temperature and period of incubation. The isolate KSB (Grz) showed the highest K solubilization index of 462.28% after 48 h of incubation at 20 °C. The maximum of 23.38 µg K/mL broth was solubilized by the isolate KSB (Grz) at 20 °C after 20 days of incubation. Based on morphological, biochemical, and molecular characterization (through the 16S rDNA approach), the isolate KSB (Grz) was identified as Mesorhizobium sp. The majority of the strains produced HCN and ammonia. The maximum indole acetic acid (IAA) (31.54 µM/mL) and cellulase (390 µM/mL) were produced by the isolate KSB (Grz). In contrast, the highest protease (525.12 µM/mL) and chitinase (5.20 µM/mL) activities were shown by standard strain Bacillus mucilaginosus and KSB (Gmr) isolate, respectively.

Growth Inhibition and Induction of Innate Immune Signaling of Chondrosarcomas with Epigenetic Inhibitors.

Chondrosarcomas are inherently resistant to chemotherapy and radiotherapy, pointing to an unmet need for new treatment options. Immune checkpoint inhibitors, which have shown remarkable promise in multiple solid cancer types, have limited efficacy in chondrosarcomas. Mutations in IDH1/2 genes, which result in progressive increases in DNA and histone methylation, are observed in 50% of conventional chondrosarcomas, suggesting that epigenetic dysregulation represents a potential barrier for tumor progression and target for therapeutic intervention. Here, we demonstrated that combined treatment of FDA-approved inhibitors of DNA methyltransferases (DNMTs) 5-aza-2'-deoxycytidine (5-aza), and histone deacetylases (HDACs) suberanilohydroxamic acid (SAHA) impaired the proliferation of chondrosarcoma cell lines in vitro and in xenograft studies. Transcriptomic analysis reveals that chondrosarcoma cells treated with 5-aza and SAHA markedly elevated the expression of IFN-stimulated genes including PD-L1, indicating that these epigenetic drugs induced a potent innate immune response. We demonstrated that 5-aza and SAHA resulted in both genomic and epigenomic instability, as shown by elevated DNA damage response and derepression of retrotransposons, respectively, which in turn activated pattern recognition receptors (PRRs) and the downstream IFN signaling pathways. Importantly, the cytotoxic effects of 5-aza and SAHA can be rescued by depletion of PRRs such as cGAS and MAVS, and potentiated by depletion of the RNA-editing enzyme ADAR1. Together, our results demonstrate preclinical activity of combined DNMT and HDAC inhibition against chondrosarcomas and suggest that targeted epigenetic therapies could represent a new therapeutic approach in the treatment of chondrosarcomas, and this is being tested in an ongoing clinical trial (NCT04340843).

Ectopic expression of a novel cold-resistance protein 1 from Brassica oleracea promotes tolerance to chilling stress in transgenic tomato.

Cold stress is considered as one of the major environmental factors that adversely affects the plant growth and distribution. Therefore, there arises an immediate need to cultivate effective strategies aimed at developing stress-tolerant crops that would boost the production and minimise the risks associated with cold stress. In this study, a novel cold-responsive protein1 (BoCRP1) isolated from Brassica oleracea was ectopically expressed in a cold susceptible tomato genotype Shalimar 1 and its function was investigated in response to chilling stress. BoCRP1 was constitutively expressed in all the tissues of B. oleracea including leaf, root and stem. However, its expression was found to be significantly increased in response to cold stress. Moreover, transgenic tomato plants expressing BoCRP1 exhibited increased tolerance to chilling stress (4 °C) with an overall improved rate of seed germination, increased root length, reduced membrane damage and increased accumulation of osmoprotectants. Furthermore, we observed increased transcript levels of stress responsive genes and enhanced accumulation of reactive oxygen species scavenging enzymes in transgenic plants on exposure to chilling stress. Taken together, these results strongly suggest that BoCRP1 is a promising candidate gene to improve the cold stress tolerance in tomato.

mTORC1 induces eukaryotic translation initiation factor 4E interaction with TOS-S6 kinase 1 and its activation.

Eukaryotic translation initiation factor 4E was recently shown to be a substrate of mTORC1, suggesting it may be a mediator of mTORC1 signaling. Here, we present evidence that eIF4E phosphorylated at S209 interacts with TOS motif of S6 Kinase1 (S6K1). We also show that this interaction is sufficient to overcome rapamycin sensitivity and mTORC1 dependence of S6K1. Furthermore, we show that eIF4E-TOS interaction relieves S6K1 from auto-inhibition due to carboxy terminal domain (CTD) and primes it for hydrophobic motif (HM) phosphorylation and activation in mTORC1 independent manner. We conclude that the role of mTORC1 is restricted to engaging eIF4E with S6K1-TOS motif to influence its state of HM phosphorylation and inducing its activation.

Fabrication of an ultra-sensitive para-nitrophenol sensor based on facile Zn-doped Er2O3 nanocomposites via an electrochemical approach.

In this study, a semiconductor-doped nanocomposite material (Zn-doped Er2O3 nano-composites) was prepared via a single-step wet-chemical technique at alkaline pH. Fourier-transform infrared spectroscopy (FT-IR), UV/Vis spectroscopy, photoluminescence spectroscopy (PL), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (XEDS), and X-ray powder diffractometry (XRD) were applied to determine the structural and morphological properties of the Zn-doped Er2O3 nanocomposite. A thin layer of aggregated Zn-doped Er2O3 nanocomposite was fabricated on the flat surface of a glassy carbon electrode (GCE) with 5% ethanolic Nafion as conducting coating binder for the development of a selective and sensitive p-nitrophenol (para-NP) capturing electrochemical probe for environmental remediation. After the fabrication of the sensor, a novel current-potential (I-V) electrochemical approach was applied to determine its selectivity and sensitivity together with all the necessary analytical parameters against para-NP. Moreover, the calibration plot was found to be linear with the linear dynamic range (LDR) of para-NP concentration. The limit of detection (LOD) at a signal-to-noise ratio of 3 (S/N ∼ 3) and sensitivity were also calculated to be 0.033 ± 0.002 pM and 28.481 × 10-2 µA µM-1 cm-2, respectively, based on the gradient of the calibration plot, and the limit of quantification (LOQ) was determined to be 0.11 ± 0.02 pM. This work demonstrates a well-known approach for the first time that can be used for the development of efficient electrochemical sensors. These sensors based on semiconductor doped nanomaterials embedded onto the GCE for the detection of toxic chemicals in an aqueous system as an environmental remediation. It can be further applied for the analysis of real environmental samples and in the healthcare field.

A New Cr3+ Electrochemical Sensor Based on ATNA/Nafion/Glassy Carbon Electrode.

A new electrochemical sensor of metal cation in an aqueous solution based on homobifunctional tridentate disulfide Schiff base and named 1,1'-(-((disulfanediylbis(2,1-phenylene))bis(azaneylylidene))bis(methaneylylidene))bis(naphthalene-2-ol) (ATNA) was easily obtained quantitatively from the condensation reaction of 2-hydroxy-1-naphthaldehyde and2-aminothiophenol, and then fully characterized by spectroscopic techniques for structure elucidation. The molecular structure of ATNA was also confirmed by a single-crystal X-ray diffraction study to reveal a new conformation in which the molecule was stabilized by the O-H…N type intramolecular hydrogen bonding interactions in both moieties. The ATNA was used as a selective electrochemical sensor for the detection of chromium ion (Cr3+). A thin film of ATNA was coated on to the flat surface of glassy carbon electrode (GCE) followed by 5 % ethanolic Nafion in order to make the modified GCE (ATNA/Nafion/GCE) as an efficient and sensitive electrochemical sensor. It was found to be very effective and selective against Cr3+ cations in the company of other intrusive heavy metal cations such as Al3+, Ce3+, Co2+, Cu2+, Ga3+, Hg2+, Mn2+, Pb2+, and Y3+. The detection limit at 3 S/N was found to be 0.013 nM for Cr3+ ions within the linear dynamic range (LDR) (0.1 nM-10.0 mM) of Cr3+ ions with r2 = 0.9579. Moreover; this work instigates a new methodology for developing the sensitive as well as selective electrochemical toxic cationic sensors in the field of environmental and health care.

Eukaryotic Initiation Factor 4E phosphorylation acts a switch for its binding to 4E-BP1 and mRNA cap assembly.

Translational regulation has invited considerable interest consequent of its circumstantial dysregulation during cancer genesis. eIF4E (Eukaryotic Initiation Factor 4E) has been identified as an important factor involved in tumor progression by way of instrumenting the convergence of oncogenic signals for up-regulation of Cap-dependent translation. In the backdrop of dramatic eIF4E over-expression in a large population of human cancers, we suggest that the tumorigenic property of eIF4E is strictly attributed to its phosphorylation state. We provide evidence that while phosphorylated eIF4E fails to be sequestered by 4E-BP1, its dephosphorylated form shows overwhelming binding with 4E-BP1 without any consideration to the state of 4E-BP1 phosphorylation to suggest that eIF4E-4EBP1 binding is governed by eIF4E phosphorylation instead of 4E-BP1. We also show that eIF4E engages in Cap-assembly formation preferably in a phosphorylation-dependent manner to suggest that eIF4E phosphorylation rather than 4E-BP1 regulates its availability for Cap-assembly.

Eukaryotic initiation factor 4E is a novel effector of mTORC1 signaling pathway in cross talk with Mnk1.

Cellular signals that influence Cap-dependent translation have assumed significant relevance in the backdrop of their enforced dysregulation during oncogenesis. Eukaryotic initiation factor 4E(eIF4E), the mRNA cap-binding protein, has emerged as a key player to facilitate tumor progression through upregulated cap-dependent translation synchronized with enhanced cell division. We provide evidence that eIF4E phosphorylation is regulated by mTORC1 by virtue of its interaction with Raptor through a novel TPTPNPP motif and consequent phosphorylation invitro and in vivo in a Rapamycin-sensitive manner. While we show that phosphorylation pattern of eIF4E responds faithfully to Rapamycin inhibition, the prolonged exposure to Rapamycin rescues the loss of eIF4E phosphorylation through Mnk1 activation. We also present evidence that eIF4E interacts with the amino terminal domain of S6K1 in a phospho-dependent manner, and this interaction is instrumental in overriding Rapamycin inhibition of S6K1. The data endorses eIF4E as a regulatory subunit that modulates the functional attributes of mTOR effectors to synchronize cap-dependent translation with growth assertion.

Eukaryotic Initiation Factor 4E (eIF4E) sequestration mediates 4E-BP1 response to rapamycin.

The cap dependent translation initiation is a tightly controlled process of cooperative ternary complex formation by 4E-BP1, eIF4E and the 5' cap of eukaryotic mRNA in response to environmental cues like glucose, nutrients and growth factor levels. Based on the well-described effects of mTORC1/rapamycin complex on 4E-BP1 phosphorylation/s, it is generally accepted that rapamycin is a global inhibitor of cap-dependent translation. We have previously shown that 4E-BP1 resistance to rapamycin was overcome by the stoichiometric abundance of S6K1. Now we present evidence that the TOS-bearing amino terminal domain of S6K1 is sufficient to relieve the rapamycin resistance of 4E-BP1 as TOS deleted variants of S6K1, active or inactive with regard to S6K1 activity failed to bring about relief of 4E-BP1 resistance to rapamycin. We also show that the reciprocal inactivation of S6K1 by abundance of 4E-BP1 gets accomplished only with intact TOS motif in the protein. The data presented in this study identifies eIF4E and not Raptor as a cellular factor responsible to regulate rapamycin sensitivity of 4E-BP1 suggesting that the phosphorylation dynamics and rapamycin sensitivity of 4E-BP1 and S6K1 are regulated independently.

Fabrication of Sb3+ sensor based on 1,1'-(-(naphthalene-2,3-diylbis(azanylylidene))bis(methanylylidene))bis(naphthalen-2-ol)/nafion/glassy carbon electrode assembly by electrochemical approach.

A new Schiff base named 1,1'-(-(naphthalene-2,3-diylbis(azanylylidene))bis (methanylylidene))bis(naphthalen-2-ol) (NDNA) derived from 2,3-naphthalenediamine and 2-hydroxy-1-naphthaldehyde was synthesized by condensation reaction and then characterized by spectroscopic techniques for structure elucidation. In addition to spectroscopic techniques, the molecular structure of NDNA was clearly confirmed by single-crystal X-ray diffraction study. A thin film of NDNA was fabricated onto glassy carbon electrode (GCE) using 5.0% ethanolic nafion solution as a conducting binder in order to develop the cationic electrochemical sensor (NDNA/nafion/GCE) for the sensing of heavy-metal cations in aqueous systems by electrochemical technique. This newly designed sensor exhibited higher sensitivity and selectivity towards antimony (Sb3+) in the presence of other interfering heavy metal cations, as well as long-term stability. Fascinating analytical parameters such as limit of detection (LOD = 0.075 nM, SNR of 3), limit of quantification (LOQ = 0.25 nM) and sensitivity (12.658 × 10-4 µA µM-1 cm-2) were calculated from the calibration curve plot, which shows a linear dynamic range (LDR) of Sb3+ ion concentration from 0.1-10.0 mM. This work presents a new approach towards the development of sensitive, efficient as well as selective toxic cationic electrochemical sensors in the environmental and healthcare fields. Hence, this newly designed NDNA/nafion/GCE presents cost-effective and efficient outcomes and can be used as a practical substitute for the efficient detection and removal of Sb3+ ions from water samples.

Continuous Versus Interrupted Sutures for Primary Cleft Palate Repair.

BACKGROUND: Cleft palate is a common congenital problem. It is traditionally surgically repaired with interrupted sutures between the ages of 6 and 18 months, with the aim of achieving closure of both nasal and oral layers. In various fields of surgery, continuous, rather than interrupted, sutures are the norm. There are no reports, however, of continuous suture repair for cleft palate. METHODS: A comparative study was designed at Clapp Hospital Lahore, to compare the effectiveness of 2 techniques. A total of 152 patients were included in the study over a period of 3 years. Per-operatively, the duration of surgery (time for nasal and oral layer closure) and the number of suture materials used were noted and compared between the 2 groups. Postoperatively, we compared the rate of wound dehiscence and fistula formation between the 2 groups. RESULTS: Out of 152 patients, 84 patients were operated on by continuous technique and 68 patients by interrupted technique. The mean duration of nasal layer closure in group A was 7.08 minutes, whereas that in group B was 11.50 minutes. The mean number of sutures required for the continuous suture group was 2.12, whereas that for the interrupted suture group was 4.59 (P < 0.05). There were no differences seen in either of the 2 postoperative outcomes compared in this study. CONCLUSION: A continuous closure technique can be utilized in palate repair, as it us more cost-effective and time-efficient.