Azadirachta indica (AI)leaf extract coated ZnO-AInanocore-shell particles for enhanced antibacterial activity against methicillin-resistantStaphylococcus aureus(MRSA).

With the rise in microbial resistance to traditional antibiotics and disinfectants, there is a pressing need for the development of novel and effective antibacterial agents. Two major approaches being adopted worldwide to overcome antimicrobial resistance are the use of plant leaf extracts and metallic nanoparticles (NPs). However, there are no reports on the antibacterial potential of NPs coated with plant extracts, which may lead to novel ways of treating infections. This study presents an innovative approach to engineer antibacterial NPs by leveraging the inherent antibacterial properties of zinc oxide NPs (ZnO NPs) in combination withAzadirachta indica(AI) leaf extract, resulting in enhanced antibacterial efficacy. ZnO NPs were synthesised by the precipitation method and subsequently coated withAIleaf extract to produce ZnO-AInanocore-shell structures. The structural and morphological characteristics of the bare and leaf extract coated ZnO NPs were analysed by x-ray diffraction and field emission scanning electron microscopy, respectively. The presence of anAIleaf extract coating on ZnO NPs and subsequent formation of ZnO-AInanocore-shell structures was verified through Fourier transform infrared spectroscopy and photoluminescence techniques. The antibacterial efficacy of both ZnO NPs and ZnO-AInanocore-shell particles was evaluated against methicillin-resistantStaphylococcus aureususing a zone of inhibition assay. The results showed an NP concentration-dependent increase in the diameter of the inhibition zone, with ZnO-AInanocore-shell particles exhibiting superior antibacterial properties, owing to the combined effect of ZnO NPs and the poly phenols present inAIleaf extract. These findings suggest that ZnO-AInanocore-shell structures hold promise for the development of novel antibacterial creams and hydrogels for various biomedical applications.

Analytical Tools and Methods for Explosive Analysis in Forensics: A Critical Review.

This review summarizes (i) compositions and types of improvised explosive devices; (ii) the process of collection, extraction and analysis of explosive evidence encountered in explosive and related cases; (iii) inter-comparison of analytical techniques; (iv) the challenges and prospects of explosive detection technology. The highlights of this study include extensive information regarding the National & International standards specified by USEPA, ASTM, and so on, for explosives detection. The holistic development of analytical tools for explosive analysis ranging from conventional methods to advanced analytical tools is also covered in this article. The most important aspect of this review is to make forensic scientists familiar with the challenges during explosive analysis and the steps to avoid them. The problems during analysis can be analyte-based, that is, interferences due to matrix or added molding/stabilizing agents, trace amount of parent explosives in post-blast samples and many more. Others are techniques-based challenges viz. specificity, selectivity, and sensitivity of the technique. Thus, it has become a primary concern to adopt rapid, field deployable, and highly sensitive techniques.

Infrared-to-visible conversion in strontium sulphate through a defect-based infrared stimulated visible emission phenomenon.

Strontium sulphate (SrSO4 ) is a defect-based photoluminescence material, generally used in thermoluminescence applications, and has been studied for infrared (IR) stimulated visible emission. The SrSO4 particles were synthesized using a precipitation method. The orthorhombic phase of SrSO4 was confirmed from the X-ray diffraction pattern and the formation of micron-sized particles was authenticated from field emission scanning electron micrographs. The elemental composition of oxygen and strontium was determined using energy-dispersive X-ray analysis measurement that confirmed the presence of V O • • and V Sr ' ' intrinsic defects in the material. Photoluminescence investigations showed the presence of various defect bands in the band gap giving rise to intrinsic luminescence in SrSO4 . The emission in the visible region was attributed to the defect band arising due to V O • • . Photoluminescence lifetime measurement confirmed the presence of stable defect states with a lifetime in microseconds. The SrSO4 sample was tested using IR lasers and a red-orange emission spot was observed from the powder sample when excited with IR lasers. The underlying principle for IR-to-visible conversion in the material is a defect-mediated phenomenon that has been described through the energy level diagram of the material.

Trends in environmental monitoring of high explosives present in soil/sediment/groundwater using LC-MS/MS.

Environmental contamination by explosives occurs due to improper handling and disposal procedures. Explosives and their transformation products pose threat to human health and the ecosystem. Trace level detection of explosives present in different environmental matrices is a challenge, due to the interference caused by matrix components and the presence of cocontaminants. Liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) is an advanced analytical tool, which is ideal for quantitative and qualitative detection of explosives and its metabolites at trace levels. This review aims to showcase the current trends in the application of LC-MS/MS for detecting explosives present in soil, sediment, and groundwater with detection limits ranging from nano to femtogram levels. Specificity and advantages of using LC-MS/MS over conventional analytical methods and various processing methods and techniques used for sample preparation are discussed in this article. Important application aspects of LC-MS/MS on environmental monitoring include site characterization and degradation evaluation. Studies on qualitative and quantitative LC-MS/MS analysis in determining the efficiency of treatment processes and contamination mapping, optimized conditions of LC and MS/MS adopted, role of different ionization techniques and mass analyzers in detection of explosives and its metabolites, relative abundance of various product ions formed on dissociation and the levels of detection achieved are reviewed. Ionization suppression, matrix effect, additive selection are some of the major factors which influence MS/MS detection. A summary of challenges and future research insights for effective utilization of this technique in the environmental monitoring of explosives are presented.

Central Retinal Vein Occlusion Following the First Dose of COVID Vaccine.

The reports of vascular adverse events in the eye following COVID-19 vaccination are infrequent. We report the case of a healthy male who developed central retinal vein occlusion in his left eye three days following administration of the first dose of Covishield vaccine. As the underlying systemic and ocular risk factors were absent and laboratory investigations were normal, vein occlusion appeared to probably result from the vaccine. The patient developed retinal hemorrhages and non-perfusion ischemic areas all over the fundus. The macular edema was reduced with intravitreal triamcinolone acetonide, but the visual gain was not much, which appears to be due to the time lag in his initial presentation to the Ophthalmology Department. A close watch should be kept for ophthalmic adverse events to have an early intervention.

Safety and Immunogenicity of a DNA SARS-CoV-2 vaccine (ZyCoV-D): Results of an open-label, non-randomized phase I part of phase I/II clinical study by intradermal route in healthy subjects in India.

BACKGROUND: ZyCoV-D is a DNA vaccine candidate, which comprises a plasmid DNA carrying spike-S gene of SARS-CoV-2 virus along with gene coding for signal peptide. The spike(S) region includes the receptor-binding domain (RBD), which binds to the human angiotensin converting Enzyme (ACE)-2 receptor and mediates the entry of virus inside the cell. METHODS: We conducted a single-center, open-label, non-randomized, Phase 1 trial in India between July 2020 and October 2020. Healthy adults aged between 18 and 55 years were sequentially enrolled and allocated to one of four treatment arms in a dose escalation manner. Three doses of vaccine were administered 28 days apart and each subject was followed up for 28 days post third dose to evaluate safety and immunogenicity. FINDINGS: Out of 126 individuals screened for eligibility. Forty-eight subjects (mean age 34·9 years) were enrolled and vaccinated in the Phase 1 study Overall, 12/48 (25%) subjects reported at least one AE (i.e. combined solicited and unsolicited) during the study. There were no deaths or serious adverse events reported in Phase 1 of the study. The proportion of subjects who seroconverted based on IgG titers on day 84 was 4/11 (36·36%), 4/12 (33·33%), 10/10 (100·00%) and 8/10 (80·00%) in the treatment Arm 1 (1 mg: Needle), Arm 2 (1 mg: NFIS), Arm 3 (2 mg: Needle) and Arm 4 (2 mg: NFIS), respectively. INTERPRETATION: ZyCoV-D vaccine is found to be safe, well-tolerated and immunogenic in the Phase 1 trial. Our findings suggest that the DNA vaccine warrants further investigation.

Molecular detection and characterization of Anaplasma platys and Ehrlichia canis in dogs from the Caribbean.

Anaplasma platys is a tick-transmitted rickettsial pathogen, which is known to be the etiologic agent for cyclic thrombocytopenia in its primary canine host. Infections with this pathogen are also reported in cats, cattle and people. Similarly, Ehrlichia canis is another tick-borne rickettsial pathogen responsible for canine monocytic ehrlichiosis and is also reported to cause infections in people. We describe infections in dogs with these two pathogens on the Caribbean island of Grenada, West Indies by detection using molecular methods. We utilized a 16S rRNA gene-based PCR assay to detect both Ehrlichia and Anaplasma species by screening 155 canine blood samples from asymptomatic dogs. We found 18.7 % of the dogs to be positive for A. platys and 16.8 % for E. canis. Samples that tested positive for A. platys were further assessed by sequence analysis targeting 16S rRNA, 23S rRNA, citrate synthase (gltA) and heat shock protein (groEL) genes. Phylogenetic analysis revealed high correlation of A. platys 16S rRNA and gltA gene sequences with the geographic origins, while 23S rRNA and groEL gene sequences clustered independent of the geographic origins. This study represents an important step in defining the widespread distribution of active rickettsial infections in Caribbean dogs with no apparent clinical signs, thus posing a high risk for canine health and to a lesser extent to humans, as most dogs in the Caribbean are free-roaming.

Development of a Multiplex PCR and Magnetic DNA Capture Assay for Detecting Six Species Pathogens of the Genera Anaplasma and Ehrlichia in Canine, Bovine, Caprine and Ovine Blood Samples from Grenada, West Indies.

Infections with tick-borne pathogens belonging to Anaplasma/Ehrlichia in various vertebrate hosts are a persistent problem resulting in nonspecific clinical signs during early infection. Diagnosis of single and multi-infections with these pathogens, causing diseases in companion/agricultural animals and people, remains a challenge. Traditional methods of diagnosis, such as microscopy and serology, have low sensitivity and specificity. Polymerase chain reaction (PCR) assays are widely used to detect early-phase infections, since these have high sensitivity and specificity. We report the development and validation of an assay involving PCR followed by magnetic capture method using species-specific oligonucleotides to detect six Anaplasma/Ehrlichia species pathogens in canine, bovine, caprine, and ovine blood samples. Overall, the assay application to 455 samples detected 30.1% (137/455) positives for one or more out of six screened pathogens. Single-pathogen infections were observed in 94.9% (130/137) of the positive samples, while co-infections were detected in 5.1% (7/137). Anaplasma marginale infection in cattle had the highest detection rate (34.4%), followed by canines positive for Anaplasma platys (16.4%) and Ehrlichia canis (13.9%). The assay aided in documenting the first molecular evidence for A. marginale in cattle and small ruminants and Ehrlichia chaffeensis and Ehrlichia ewingii in dogs in the Caribbean island of Grenada.

Identification and analysis of organic explosives from post-blast debris by nuclear magnetic resonance.

The growing threat of terrorism has triggered an urgent need to find effective ways to improve the analysis of explosives. This will aid forensic scientists in analysing the post-blast debris, which in turn helps the law enforcement agencies to frame suitable regulations. Analysis of post-blast debris is challenging as it hosts a massive amount of complexity. There are various techniques reported till date such as mass spectrometry, gas chromatography, high-performance liquid chromatography, Fourier transform infrared spectroscopy, and Raman spectroscopy for the analysis of post-blast residues. However, none of them has been able to identify the structural composition of the explosives. The current research study focuses on identifying the structural composition of the explosives from the post-blast debris using the nuclear magnetic resonance (NMR) technology. The post-blast analytes were extracted from soil samples, cleaned by the solid phase extraction (SPE) method and were rapidly analysed by the nuclear magnetic resonance spectrometer. This paper reports the identification of nitro organic explosives such as pentaerythritol tetranitrate (PETN), trinitrotoluene (TNT) and 2,4,6-trinitrophenylmethylnitramine (tetryl) in post-blast debris by 400 MHz nuclear magnetic resonance spectrometer.

Molecular detection and genetic characterization of Arcobacter butzleri isolated from red-footed pet tortoises suspected for Campylobacter spp. from Grenada, West Indies.

The aim of the study was to detect and genetically characterize Arcobacter butzleri in pet red-footed tortoises suspected for Campylobacter spp., using molecular techniques. A written consent from tortoise owners was obtained, after explaining the advantages of the research to tortoise owners of Grenada. Fecal samples were collected from 114 tortoises from five parishes of the country and cultured for Campylobacter spp. using selective culture techniques. A. butzleri was isolated from 4.39% of pet tortoises. Total thirteen isolates were obtained; all identified as A. butzleri by a universal and a species-specific Polymerase Chain Reaction (PCR) and direct sequencing. Genetic characterization of these isolates was performed based on Enterobacterial repetitive intergenic consensus PCR (ERIC-PCR) that generated eight different genetic fingerprints with a discriminatory power of 0.91. Campylobacter species were not detected molecularly in any of the culture-positive samples. This is the first report of infection of pet tortoises in Grenada, West Indies with A. butzleri. This study emphasizes on the risk of zoonotic transmission of A. butzleri by exotic pets, which is a serious concern for public health.

Toxicity of polyhalogenated dibenzo-p-furans in the light of nucleic acid bases interaction.

Quantitative structure-activity relationship (QSAR) investigation utilizing quantum chemical descriptors under density functional theory is performed to predict the toxicity (pEC50) of a series of polyhalogenated dibenzo-p-furans (PHDFs). PHDFs are very important concern to the researchers due to their presence and diverse effects in the environment. A successful two parameter QSAR model is developed with a combination of a global descriptor known as charge transfer (ΔN) between toxins and biosystem and a local descriptor as Fukui function (fmax+) for maximum nucleophilic attack at the toxin site. A systematic analysis is performed to identify the electron donation/acceptance nature of the considered PHDF compounds with the choice of a model biosystems comprising five different nucleic acid bases, namely Adenine, Thymine, Guanine, Cytosine and Uracil to identify proper ΔN descriptor. Accordingly, PHDFs are found to be electron acceptors with maximum charge transfer from Guanine and therefore, ΔNG is utilized as the charge transfer parameter for all the toxins in the present work. The selected combination of global and local descriptors (ΔNG andfmax+) are found to predict 93% of the observed toxicity (pEC50) of the PHDFs. The developed QSAR model is tested for two different test sets: PHDFs and polyhalogenated biphenyls (PHBs) with about 90% of prediction of their toxicity values, which confirms the importance of the selected descriptors.

Identification of a novel trafficking pathway exporting a replication protein, Orc2 to nucleus via classical secretory pathway in Plasmodium falciparum.

Malaria parasites use an extensive secretory pathway to traffic a number of proteins within itself and beyond. In higher eukaryotes, Endoplasmic Reticulum (ER) membrane bound transcription factors such as SREBP are reported to get processed en route and migrate to nucleus under the influence of specific cues. However, a protein constitutively trafficked to the nucleus via classical secretory pathway has not been reported. Herein, we report the presence of a novel trafficking pathway in an apicomplexan, Plasmodium falciparum where a homologue of an Origin Recognition Complex 2 (Orc2) goes to the nucleus following its association with the ER. Our work highlights the unconventional role of ER in protein trafficking and reports for the first time an ORC homologue getting trafficked through such a pathway to the nucleus where it may be involved in DNA replication and other ancillary functions. Such trafficking pathways may have a profound impact on the cell biology of a malaria parasite and have significant implications in strategizing new antimalarials.

Initial development and preliminary evaluation of a multiplex bead assay to detect antibodies to Ehrlichia canis, Anaplasma platys, and Ehrlichia chaffeensis outer membrane peptides in naturally infected dogs from Grenada, West Indies.

Tick-borne bacteria, Ehrlichia canis, Anaplasma platys, and Ehrlichia chaffeensis are significant pathogens of dogs worldwide, and coinfections of E. canis and A. platys are common in dogs on the Caribbean islands. We developed and evaluated the performance of a multiplex bead-based assay to detect antibodies to E. canis, A. platys, and E. chaffeensis peptides in dogs from Grenada, West Indies, where E. canis and A. platys infections are endemic. Peptides from outer membrane proteins of P30 of E. canis, OMP-1X of A. platys, and P28-19/P28-14 of E. chaffeensis were coupled to magnetic beads. The multiplex peptide assay detected antibodies in dogs experimentally infected with E. canis and E. chaffeensis, but not in an A. platys experimentally infected dog. In contrast, the multiplex assay and an in-house enzyme-linked immunosorbent assay (ELISA) detected A. platys antibodies in naturally infected Grenadian dogs. Following testing of 104 Grenadian canine samples, multiplex assay results had good agreement with commercially available ELISA and immunofluorescent assay for E. canis antibody-positive dogs ( K values of 0.73 and 0.84), whereas A. platys multiplex results had poor agreement with these commercial assays ( K values of -0.02 and 0.01). Prevalence of seropositive E. canis and A. platys Grenadian dogs detected by the multiplex and commercial antibody assays were similar to previous reports. Although the multiplex peptide assay performed well in detecting the seropositive status of dogs to E. canis and had good agreement with commercial assays, better antigen targets are necessary for the antibody detection of A. platys.

Structural investigation and inhibitory response of halide on phosphoserine aminotransferase from Trichomonas vaginalis.

BACKGROUND: Phosphoserine aminotransferase (PSAT) catalyses the second reversible step of the phosphoserine biosynthetic pathway in Trichomonas vaginalis, which is crucial for the synthesis of serine and cysteine. METHODS: PSAT from T. vaginalis (TvPSAT) was analysed using X-ray crystallography, enzyme kinetics, and molecular dynamics simulations. RESULTS: The crystal structure of TvPSAT was determined to 2.15Å resolution, and is the first protozoan PSAT structure to be reported. The active site of TvPSAT structure was found to be in a closed conformation, and at the active site PLP formed an internal aldimine linkage to Lys 202. In TvPSAT, Val 340 near the active site while it is Arg in most other members of the PSAT family, might be responsible in closing the active site. Kinetic studies yielded Km values of 54 µM and 202 µM for TvPSAT with OPLS and AKG, respectively. Only iodine inhibited the TvPSAT activity while smaller halides could not inhibit. CONCLUSION: Results from the structure, comparative molecular dynamics simulations, and the inhibition studies suggest that iodine is the only halide that can bind TvPSAT strongly and may thus inhibit the activity of TvPSAT. The long loop between ß8 and α8 at the opening of the TvPSAT active site cleft compared to other PSATs, suggests that this loop may help control the access of substrates to the TvPSAT active site and thus influences the enzyme kinetics. GENERAL SIGNIFICANCE: Our structural and functional studies have improved our understanding of how PSAT helps this organism persists in the environment.

Critical roles for Rictor/Sin1 complexes in interferon-dependent gene transcription and generation of antiproliferative responses.

We provide evidence that type I IFN-induced STAT activation is diminished in cells with targeted disruption of the Rictor gene, whose protein product is a key element of mTOR complex 2. Our studies show that transient or stable knockdown of Rictor or Sin1 results in defects in activation of elements of the STAT pathway and reduced STAT-DNA binding complexes. This leads to decreased expression of several IFN-inducible genes that mediate important biological functions. Our studies also demonstrate that Rictor and Sin1 play essential roles in the generation of the suppressive effects of IFNα on malignant erythroid precursors from patients with myeloproliferative neoplasms. Altogether, these findings provide evidence for critical functions for Rictor/Sin1 complexes in type I IFN signaling and the generation of type I IFN antineoplastic responses.

Correlation of visual functions with macular thickness in primary open angle glaucoma.

AIM: The aim of this study was to establish a correlation between macular thickness on optical coherence tomography (OCT) and 2 visual functions (visual acuity and contrast sensitivity [CS]) in established cases of primary open angle glaucoma (POAG). MATERIALS AND METHODS: A total of 50 consecutive patients of established POAG between 40 years and 70 years of age attending the glaucoma clinic of a tertiary care eye center in North India were enrolled for this cross-sectional study. Best corrected visual acuity (BCVA), CS and macular thickness by spectral-domain-OCT (Cirrus HD-OCT, CarlZeiss, Germany) were evaluated. STATISTICAL ANALYSIS: The groups were compared together by one factor analysis of variance and the significance of mean difference between the groups was done by Newman-Keuls test. RESULTS: Newman-Keuls test revealed a direct relationship of macular thickness to BCVA and CS (P < 0.05). CONCLUSION: BCVA and CS are directly related to the macular thickness on OCT.

Essential role for the Mnk pathway in the inhibitory effects of type I interferons on myeloproliferative neoplasm (MPN) precursors.

The mechanisms of generation of the antineoplastic effects of interferons (IFNs) in malignant hematopoietic cells remain to be precisely defined. We examined the activation of type I IFN-dependent signaling pathways in malignant cells transformed by Jak2V617F, a critical pathogenic mutation in myeloproliferative neoplasms (MPNs). Our studies demonstrate that during engagement of the type I IFN receptor (IFNAR), there is activation of Jak-Stat pathways and also engagement of Mnk kinases. Activation of Mnk kinases is regulated by the Mek/Erk pathway and is required for the generation of IFN-induced growth inhibitory responses, but Mnk kinase activation does not modulate IFN-regulated Jak-Stat signals. We demonstrate that for type I IFNs to exert suppressive effects in malignant hematopoietic progenitors from patients with polycythemia vera, induction of Mnk kinase activity is required, as evidenced by studies involving pharmacological inhibition of Mnk or siRNA-mediated Mnk knockdown. Altogether, these findings provide evidence for key and essential roles of the Mnk kinase pathway in the generation of the antineoplastic effects of type I IFNs in Jak2V617F-dependent MPNs.

Sprouty proteins are negative regulators of interferon (IFN) signaling and IFN-inducible biological responses.

Interferons (IFNs) have important antiviral and antineoplastic properties, but the precise mechanisms required for generation of these responses remain to be defined. We provide evidence that during engagement of the Type I IFN receptor (IFNR), there is up-regulation of expression of Sprouty (Spry) proteins 1, 2, and 4. Our studies demonstrate that IFN-inducible up-regulation of Spry proteins is Mnk kinase-dependent and results in suppressive effects on the IFN-activated p38 MAP kinase (MAPK), the function of which is required for transcription of interferon-stimulated genes (ISGs). Our data establish that ISG15 mRNA expression and IFN-dependent antiviral responses are enhanced in Spry1,2,4 triple knock-out mouse embryonic fibroblasts, consistent with negative feedback regulatory roles for Spry proteins in IFN-mediated signaling. In other studies, we found that siRNA-mediated knockdown of Spry1, Spry2, or Spry4 promotes IFN-inducible antileukemic effects in vitro and results in enhanced suppressive effects on malignant hematopoietic progenitors from patients with polycythemia vera. Altogether, our findings demonstrate that Spry proteins are potent regulators of Type I IFN signaling and negatively control induction of Type I IFN-mediated biological responses.

Autophagic degradation of the BCR-ABL oncoprotein and generation of antileukemic responses by arsenic trioxide.

We provide evidence that arsenic trioxide (As(2)O(3)) targets the BCR-ABL oncoprotein via a novel mechanism involving p62/SQSTM1-mediated localization of the oncoprotein to the autolysosomes and subsequent degradation mediated by the protease cathepsin B. Our studies demonstrate that inhibitors of autophagy or cathepsin B activity and/or molecular targeting of p62/SQSTM1, Atg7, or cathepsin B result in partial reversal of the suppressive effects of AS(2)O(3) on BCR-ABL expressing leukemic progenitors, including primitive leukemic precursors from chronic myelogenous leukemia (CML) patients. Altogether, these findings indicate that autophagic degradation of BCR-ABL is critical for the induction of the antileukemic effects of As(2)O(3) and raise the potential for future therapeutic approaches to target BCR-ABL expressing cells by modulating elements of the autophagic machinery to promote BCR-ABL degradation.

Regulatory effects of programmed cell death 4 (PDCD4) protein in interferon (IFN)-stimulated gene expression and generation of type I IFN responses.

The precise mechanisms by which the activation of interferon (IFN) receptors (IFNRs) ultimately controls mRNA translation of specific target genes to induce IFN-dependent biological responses remain ill defined. We provide evidence that IFN-α induces phosphorylation of programmed cell death 4 (PDCD4) protein on Ser67. This IFN-α-dependent phosphorylation is mediated by either the p70 S6 kinase (S6K) or the p90 ribosomal protein S6K (RSK) in a cell-type-specific manner. IFN-dependent phosphorylation of PDCD4 results in downregulation of PDCD4 protein levels as the phosphorylated form of PDCD4 interacts with the ubiquitin ligase ß-TRCP (ß-transducin repeat-containing protein) and undergoes degradation. This process facilitates IFN-induced eukaryotic translation initiation factor 4A (eIF4A) activity and binding to translation initiation factor eIF4G to promote mRNA translation. Our data establish that PDCD4 degradation ultimately facilitates expression of several ISG protein products that play important roles in the generation of IFN responses, including IFN-stimulated gene 15 (ISG15), p21(WAF1/CIP1), and Schlafen 5 (SLFN5). Moreover, engagement of the RSK/PDCD4 pathway by the type I IFNR is required for the suppressive effects of IFN-α on normal CD34(+) hematopoietic precursors and for antileukemic effects in vitro. Altogether, these findings provide evidence for a unique function of PDCD4 in the type I IFN system and indicate a key regulatory role for this protein in mRNA translation of ISGs and control of IFN responses.