Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 96
Filter
Add more filters











Publication year range
1.
Adv Sci (Weinh) ; 11(35): e2404993, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38994888

ABSTRACT

Metal-organic frameworks (MOFs) have emerged as promising materials for triboelectric nanogenerators (TENGs), but the effects of ligand choice on triboelectric charge remain underexplored. Hence, this paper demonstrates the effect of single, binary, and ternary ligands on TENG performance of cobalt/cerium-based (Co─Ce) bimetallic MOFs utilizing 2-methylimidazole (2Melm), terephthalic acid (BDC), and benzene tricarboxylic acid (BTC) as ligands. The detailed structural characterization revealed that varying ligand chemistries led to distinct MOF features affecting TENG performance. Single ligand bimetallic MOFs (designated as CoCe-2MeIm, CoCe-BDC, CoCe-BTC) has lower performance than binary ligand (designated as CoCe-2MeIm-BDC, CoCe-2MeIm-BTC, CoCe-BDC-BTC) and ternary ligand MOFs (designated as CoCe-2MeIm-BDC-BTC). Among all, the binary ligand MOF, CoCe-2MeIm-BTC, shows the best results (598 V, 26.7 µA) due to the combined effect of imidazole ring and (─COO─) groups. This is attributed to lone pairs on nitrogen atoms and a delocalized π-electron system in imidazole system in this material. CoCe-BTC has the lowest results (31 V, 3.2 µA) due to the bulkier nature of the electron-withdrawing (─COO─) groups and their impact on the π-electron system of the benzene ring. This study showcases the potential of ligand chemistry manipulation to control triboelectric charge and thereby enhance MOF-based TENG performance.

2.
Invest Ophthalmol Vis Sci ; 65(6): 36, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38916883

ABSTRACT

Purpose: Neutrophils are known mediators of innate immunity, yet their effector function in herpesvirus infections remains poorly understood. Here, we elucidate the mechanistic action and pivotal role of neutrophil extracellular traps (NETs) during herpes simplex virus type 1 (HSV-1) ocular infection. Methods: Neutrophils were collected from mice for HSV-1 infection, fluorescence imaging, and immunoblotting assay. Tear samples from healthy subjects and patients with HSV-1 and mice were collected at L. V. Prasad Eye Institute, India, and at the University of Illinois, USA, respectively. For the in vivo study, C57BL/6 mice as well as diversity outbred mice were infected with HSV-1 (McKrae strain) followed by tear fluid collection at various time points (0-10 days). Samples were used for Flow cytometry, ELISA, and immunofluorescence assay. Human transcriptomic profile of keratitis dataset was used evaluate NETosis signaling pathways. We also performed neutrophil depletion studies. Results: Our data revealed a discernible temporal NET formation (NETosis) predominantly in the infected eye, across normal and diversity outbred murine models and human cases of HSV-1 infection. HSV-1 instigates swift NETosis governed by caspase-1 activation and myeloperoxidase secretion. Distinct accumulations of neutrophils, remaining unengaged in NET release in the contralateral eye post-infection, hinting at a proactive defensive posture in the uninfected eye. Moreover, neutrophil depletion accentuated ocular pathology, augmented viral load, and escalated disease scores, substantiating the protective effects of NETs in curtailing viral replication. Conclusions: Our report uncovers a previously unexplored mechanism of NETosis through pro-inflammatory cell death in response to ocular HSV-1 infection, and HPSE up-regulation, identifying new avenues for future studies.


Subject(s)
Disease Models, Animal , Extracellular Traps , Herpesvirus 1, Human , Keratitis, Herpetic , Mice, Inbred C57BL , Neutrophils , Tears , Animals , Mice , Extracellular Traps/metabolism , Herpesvirus 1, Human/physiology , Keratitis, Herpetic/virology , Keratitis, Herpetic/immunology , Keratitis, Herpetic/metabolism , Humans , Neutrophils/immunology , Tears/virology , Tears/metabolism , Female , Flow Cytometry , Enzyme-Linked Immunosorbent Assay , Immunity, Innate , Eye Infections, Viral/virology , Eye Infections, Viral/metabolism
3.
Adv Mater ; 36(19): e2311029, 2024 May.
Article in English | MEDLINE | ID: mdl-38299366

ABSTRACT

Practical application of triboelectric nanogenerators (TENGs) has been challenging, particularly, under harsh environmental conditions. This work proposes a novel 3D-fused aromatic ladder (FAL) structure as a tribo-positive material for TENGs, to address these challenges. The 3D-FAL offers a unique materials engineering platform for tailored properties, such as high specific surface area and porosity, good thermal and mechanical stability, and tunable electronic properties. The fabricated 3D-FAL-based TENG reaches a maximum peak power density of 451.2 µW cm-2 at 5 Hz frequency. More importantly, the 3D-FAL-based TENG maintains stable output performance under harsh operating environments, over wide temperature (-45-100 °C) and humidity ranges (8.3-96.7% RH), representing the development of novel FAL for sustainable energy generation under challenging environmental conditions. Furthermore, the 3D-FAL-based TENG proves to be a promising device for a speed monitoring system engaging reconstruction in virtual reality in a snowy environment.

4.
J Anim Breed Genet ; 141(4): 415-424, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38284302

ABSTRACT

The study was done to determine additive, maternal and common permanent environmental effects and best-suited model for some production traits using six univariate animal models that differed in the (co)variance components fitted to assess the importance of maternal effect using likelihood ratio test in Murrah buffaloes. Data from 614 Murrah buffaloes related to production traits were collected from history pedigree sheets maintained at the buffalo farm, Department of Livestock Production and Management (LPM), LUVAS, Hisar. The production traits under this study were 305 days milk yield (305DMY), peak yield (PY), lactation length (LL), dry period (DP), lactation milk yield (LMY) and wet average (WA). The heritability estimates were in the range of 0.33-0.44 for 305DMY, 0.25-0.51 for PY, 0.05-0.13 for LL, 0.03-0.23 for DP, 0.17-0.40 for LMY and 0.37-0.66 for WA. Model 1 was considered best for most of the traits, viz., 305DMY, PY, LL, LMY and WA followed by model 2 for DP. Covariance and correlated values within the traits caused inflation of heritability in model 3 and model 6. The maximum covariance between the additive and maternal effect was found in trait LMY, which was 14,183.90 in model 3 and the minimum value was also reported in the same trait for model 6, valued at -3522.37. Multivariate analysis showed that all production traits were moderate to high and positively correlated with each other except for DP, which was low and negative genetic and phenotypic correlated. Spearman's rank correlation coefficients of breeding value among all six models were high and significant, ranged from 0.78 to 1.00 for all the traits except DP, therefore any of the models could be taken into account depending upon the availability of data.


Subject(s)
Buffaloes , Lactation , Animals , Buffaloes/genetics , Buffaloes/physiology , Female , Lactation/genetics , Milk/metabolism , Phenotype , Models, Genetic , Breeding , Maternal Inheritance/genetics , Quantitative Trait, Heritable
5.
Reprod Domest Anim ; 59(1): e14526, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38268210

ABSTRACT

The research utilized data from 662 Murrah buffaloes meticulously recorded over 24 years (1996-2019) from historical pedigree sheets maintained at the buffalo farm of the Department of Livestock Production and Management (LPM) at Lala Lajpat Rai University of Veterinary and Animal Sciences (LUVAS), Hisar. A series of six univariate animal models were employed to calculate estimates of (co)variance components and heritability for first lactation reproduction traits. Among these models, Model 2 was identified as the best fit for age at first calving (AFC) and calving interval (CI), while Model 1 proved optimal for service period (SP) and conception rate (CR). The heritability estimates for AFC, SP, CR and CI across the models were ranged between 0.11 and 0.32, 0.01 and 0.03, 0.05 and 0.06, and 0.01 and 0.06, respectively. Maternal effects (m2 ) were observed in AFC and CI, ranging from 0.10 to 0.20 and 0.01 to 0.03, respectively. Across all three traits, there was a consistent negative genetic correlation (-0.75 to -0.92) between direct additive and maternal effects. The breeding values for AFC, SP, CR and CI varied within specific ranges from -32.85 to 44.33 days, -15.61 to 28.42 days, -7.41 to 6.48% and -20.64 to 35.79 days, respectively. Significantly, Spearman's rank correlation analysis revealed highly significant relationships (p < .01) between the breeding values of different models, indicating strong and consistent associations within these traits. These findings underscore the stable and reliable connections observed within the breeding values for these essential reproductive traits across the various models used in the study. The majority of reproductive traits showed favourable negative trends, indicating a positive outcome. A decrease in AFC, SP and CI suggests an extended economic life for the animals. Additionally, the upward trends in CR reflect positive indications of effective management practices and skilled operational procedures.


Subject(s)
Bison , Animals , Female , Farms , Fertilization , Lactation/genetics , Reproduction/genetics
6.
Trop Anim Health Prod ; 56(1): 17, 2023 Dec 18.
Article in English | MEDLINE | ID: mdl-38110582

ABSTRACT

The objective of the present study was to assess the seminal parameters of rooster and its association with fertility traits (%), viz., hatchability of the fertile egg set (HFES), hatchability of the total egg set (HTES), and fertility (FERT). The data records pertained to traits of interest were obtained from various registers maintained at Poultry farm, of the Department of Animal Genetics and Breeding, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar (India). The relationship between seminal and fertility characteristics was investigated using regression analysis and correlation. Moreover, the efficacy of seminal characteristics to distinguish between roosters with low and high fertility traits was evaluated using linear discriminant analysis (LDA). The findings showed that reproductive traits and seminal characteristics were significantly (P < 0.05) correlated. The LDA showed that the seminal parameters can effectively separate the roosters into those with high and poor reproductive features. It was revealed from LDA that seminal features showed higher classification accuracy for FERT (80.77%). Hatchability is dependent on eggs that have been artificially incubated; hence, these crucial traits are comparatively weaker for HTES (65.38%) and HFES (67.31%). Cross-validation of the seminal parameter LDA corroborated the aforementioned and related conclusions. It is suggested that the studied LDA function may be utilised to choose genotypes with improved reproductive traits based on seminal variables.


Subject(s)
Chickens , Ovum , Animals , Male , Chickens/genetics , Fertility/genetics , Reproduction , Genotype
7.
Data Brief ; 51: 109743, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38020443

ABSTRACT

The real-time air-writing multilingual datasets are widely used for several purposes, such as handwriting character or numeral pattern recognition. The air-writing systems are commonly used in operation theatres, online education systems, banking sectors, reservation counters, etc. However, the air-written numeral datasets are less for Devanagari and English languages needed for detecting patterns. Therefore, the present article introduces novel datasets written in the air for Devanagari and English. In addition, this article proposes a systematic novel strategy to collect the air-written multilingual numeral dataset from 100 individuals ranging in 20-40 age groups. The Devanagari and English 0-9 digits were ten times written in the air by every individual resulting in 10,000 images for each language. Thus, 20,000 images were generated and stored in the databases. The proposed dataset is freely available and could be a good resource for pattern recognition research.

8.
Invest Ophthalmol Vis Sci ; 64(14): 41, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-38015175

ABSTRACT

Purpose: The objective of this study was to explore the ocular and systemic outcomes of herpes simplex virus type 1 (HSV-1) infection in guinea pigs, to monitor the spontaneous reactivation of the virus, and to assess the effectiveness of various treatments, drawing comparisons to conventional rabbit models. Methods: Guinea pigs and rabbits were infected in the right corneas with differing doses and strains of HSV-1. Observations were made over a 71-day period, focusing on comparing ocular lesions, viral shedding patterns, and weight loss between the two animal models. Postinfection, the effectiveness of trifluridine ophthalmic drops, oral acyclovir, and valacyclovir was evaluated. The confirmation of viral infection was done through virus titer assay, fluorescein staining, and corneal imaging. Results: Guinea pigs and rabbits manifested symptoms akin to human herpes stromal keratitis (HSK) when exposed to varying titers of viral suspension. Regardless of the initial viral load, all guinea pig groups demonstrated comparable ocular pathology, witnessing conditions like blepharitis and conjunctivitis within 3 days, progressing to severe conditions, including total corneal opacification and necrotizing keratitis. Tear film collection revealed nonsignificant differences in viral plaques between all groups. Notably, guinea pigs in the low-infection group experienced the most weight loss, although without significant differences. The replication of the same experiment on rabbits yielded consistent results in disease pathology across different groups, with occurrences of blepharitis and conjunctivitis. Interestingly, after initial resolution, guinea pigs presented a more frequent and broadly observed increase in disease score and corneal opacity, a phenomenon rarely seen in rabbits within the same timeframe. The effectiveness of 1% trifluridine was observed in mitigating ocular HSV-1 disease in both species, whereas oral acyclovir and valacyclovir were found to be detrimental and ineffective in guinea pigs but not in rabbits. Conclusions: This study demonstrates the potential suitability of guinea pigs as new models for ocular HSV-1 investigations, filling a critical preclinical void of models capable of showcasing spontaneous HSV reactivation in the eye. The observed similarities and differences in the reactions of guinea pigs and rabbits to HSV-1 infection and treatments provide crucial insights, laying the foundation for future studies on ocular HSV pathogenesis, latency, and improved treatment options.


Subject(s)
Antiviral Agents , Blepharitis , Conjunctivitis , Herpes Simplex , Herpesvirus 1, Human , Trifluridine , Animals , Guinea Pigs , Humans , Rabbits , Acyclovir , Blepharitis/drug therapy , Conjunctivitis/drug therapy , Cornea , Herpes Simplex/drug therapy , Trifluridine/therapeutic use , Valacyclovir , Weight Loss , Antiviral Agents/therapeutic use
9.
Sci Adv ; 9(17): eadf3977, 2023 04 28.
Article in English | MEDLINE | ID: mdl-37115924

ABSTRACT

Limited knowledge exists on exogenous DNA virus reinfections. Herpes simplex virus-1 (HSV-1), a prototype DNA virus, causes multiple human diseases including vision-threatening eye infections. While reinfection with an exogenous HSV-1 strain is considered plausible, little is known about the underlying mechanisms governing its pathophysiology in a host. Heparanase (HPSE), a host endoglycosidase, when up-regulated by HSV-1 infection dictates local inflammatory response by destabilizing tissue architecture. Here, we demonstrate that HSV-1 reinfection in mice causes notable pathophysiology in wild-type controls compared to the animals lacking HPSE. The endoglycosidase promotes infected cell survival and supports a pro-disease environment. In contrast, lack of HPSE strengthens intrinsic immunity by promoting cytokine expression, inducing necroptosis of infected cells, and decreasing leukocyte infiltration into the cornea. Collectively, we report that immunity from a recent prior infection fails to abolish disease manifestation during HSV-1 reinfection unless HPSE is rendered inactive.


Subject(s)
Herpes Simplex , Herpesvirus 1, Human , Humans , Animals , Mice , Reinfection , Glucuronidase/genetics , Glucuronidase/metabolism
10.
Comput Struct Biotechnol J ; 21: 1030-1040, 2023.
Article in English | MEDLINE | ID: mdl-36733705

ABSTRACT

The structural diversity of metazoic heparan sulfate (HS) composed of unique sulfated domains is remarkably preserved among various vertebrates and invertebrate species. Interestingly the sulfated moieties of HS have been known as the key determinants generating extraordinary ligand binding sites in the HS chain to regulate multiple biological functions and homeostasis. One such ligand for 3-O sulfation in the HS chain is a glycoprotein D (gD) from an ancient herpesvirus, herpes simplex virus (HSV). This interaction between gD and 3-O sulfated HS leads to virus-cell fusion to promote HSV entry. It is quite astonishing that HSV-1, which infects two-thirds of the world population, is also capable of causing severe diseases in primates and non-primates including primitive zebrafish. Supporting evidence that HSV may cross the species barrier comes from the fact that an enzymatic modification in HS encoded by 3-O sulfotransferase-3 (3-OST-3) from a vertebrate zoonotic species enhances HSV-1 infectivity. The latter phenomenon suggests the possible role of sulfated-HS as an entry receptor during reverse zoonosis, especially during an event when humans encounter domesticated animals in proximity. In this mini-review, we explore the possibility that structural diversity in HS may have played a substantial role in species-specific adaptability for herpesviruses in general including their potential role in promoting cross-species transmission.

11.
Anim Biotechnol ; 34(1): 39-55, 2023 Feb.
Article in English | MEDLINE | ID: mdl-34120566

ABSTRACT

Bos indicus breed Sahiwal, famous for its optimum performance, has so far been genetically improved for performance traits based on phenotypic records and the genomic knowhow regarding genes, regions and biological processes underlying the complex quantitative traits is lacking. In this context, a Genome-wide Association Study was performed for fertility and growth traits in Sahiwal cattle to shed light on its genomic profile. A total of 46 SNPs were found associated with the traits at genome-wide suggestive threshold of P ≤ 10-4. USP32, LRPPRC, PLA2G10, RRN3 and ASAP1 were identified as putative candidate genes for body weight at different ages. However, several genes mapped for growth traits like GREB1, PLA2G10, RAD51C, BIRC6, TEX14 and PEBP4 had significant physiological underpinnings in determining fertility of the animals. Moreover, Quantitative trait loci (QTL) identification revealed potential overlaps with the already reported QTLs for both fertility and growth for most of the traits. Further, candidate SNP enrichment analysis revealed an enriched biological process for birth weight with a significant reproductive role. Based on the findings, genetic linkages underlying fertility and growth could be discerned in Sahiwal population and may be utilized for improving fertility traits in future.


Subject(s)
Biological Phenomena , Genome-Wide Association Study , Cattle , Animals , Genome-Wide Association Study/veterinary , Genotype , Fertility/genetics , Quantitative Trait Loci , Phenotype , Genetic Linkage , Polymorphism, Single Nucleotide
12.
Antiviral Res ; 208: 105454, 2022 12.
Article in English | MEDLINE | ID: mdl-36334637

ABSTRACT

Herpes simplex virus type-1 (HSV1) exploits cellular machinery for its own replicative advantage. Current treatment modalities against HSV1 cause toxicity and drug resistance issues. In the search for alternative forms of treatment, we have uncovered a small molecule, BX795, as a candidate drug with strong antiviral potential owing to its multitargeted mode of action. In this study, we show that in addition to a previously known mechanism of action, BX795 can directly interact with the proviral host factor protein kinase C (PKC) in silico. When administered to HSV1 or mock infected human corneal epithelial (HCE) cells, BX795 significantly reduces the protein level and perinuclear localization of proviral PKC-α and PKC-ζ isoforms. This activity closely mimics that of a known PKC inhibitor, Bisindolylmaleimide I (BIM I), which also inhibits viral replication. Taken together our studies demonstrate a previously unknown mechanism by which BX795 exerts its antiviral potential.


Subject(s)
Herpes Simplex , Herpesviridae Infections , Herpesvirus 1, Human , Humans , Herpes Simplex/drug therapy , Herpesviridae Infections/drug therapy , Antiviral Agents/therapeutic use , Protein Kinase C/metabolism
13.
Trends Microbiol ; 30(12): 1128-1130, 2022 12.
Article in English | MEDLINE | ID: mdl-36272886

ABSTRACT

In a recent article, Gao et al. diversify our knowledge of prokaryotic innate immunity by characterizing a novel bacterial defense system that utilizes nucleotide-binding oligomerization-like receptors (NLRs) for recognizing phage proteins.


Subject(s)
Bacteriophages , Bacteriophages/genetics , Immunity, Innate , Carrier Proteins , Receptors, Pattern Recognition
15.
mBio ; 13(5): e0219422, 2022 10 26.
Article in English | MEDLINE | ID: mdl-36043789

ABSTRACT

Herpes simplex virus type-1 (HSV-1) infections are known to alter the host metabolism for efficient propagation in vitro. However, in vivo metabolic perturbations upon prolonged HSV-1 infection remain poorly understood. We used high-resolution liquid chromatography coupled with mass spectrometry (LC-MS) and functional assays to determine the state of the trigeminal ganglion (TG) tissue metabolism upon prolonged corneal HSV-1 infection in a murine model. The metabolomics data indicated significant alterations in the host metabolic profile. After HSV-1 infection, the TG microenvironment assumed downregulation of central carbon metabolism and nucleotide synthesis pathways. We validated our observations using in vitro and ex vivo models through targeted inhibition of crucial metabolic polyamine pathways identified in our metabolomics screen. Our findings collectively suggested that HSV-1 infection altered the host metabolic product regulations that limit the energy and macromolecular precursors required for viral replication. IMPORTANCE The more severe ocular pathologies associated with HSV-1 infection are significant vision loss, ocular morbidity, and herpetic keratitis. The current clinical landscape lacks curative drugs and vaccines against HSV-1, a heavy burden associated with this neurotropic, ubiquitous pathogen. The virus is notoriously successful in establishing latency in the host TG, where it remains dormant with periodic reactivations in response to various stimuli like stress and immunosuppression. Metabolic perturbations in tissue microenvironment likely aid the virus in establishing its latent state along with subsequent reactivations yet remain poorly characterized. Here, we used mass spectrometry coupled with statistical data analysis to study the host metabolome in the TG during HSV-1 infection and identify metabolites that likely regulate infection.


Subject(s)
Herpes Simplex , Herpesvirus 1, Human , Keratitis, Herpetic , Mice , Animals , Herpesvirus 1, Human/physiology , Trigeminal Ganglion , Virus Replication , Cornea , Polyamines , Carbon , Nucleotides , Virus Latency/physiology
16.
Poult Sci ; 101(4): 101766, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35240355

ABSTRACT

This study was conducted to evaluate 8 mathematical models, namely, Logistic (LM), Morgqan Mercer Flodin (MMF), Polynomial Fit (PF), Rational Function (RF), Sinusoidal Fit (SF), Quadratic fit (QF), Gompertz function (GF), and Modification Compartmental Model (MCM) fitted to weekly egg production and egg weight of synthetic White Leghorn (SWL) population 21 to 40 wk of age of 5 generations (2015-16 to 2019-20). The relevant data for the present investigation were collected from SWL population, maintained in the department of Animal Genetics and Breeding, LUVAS, Hisar (India). The efficiency or reliability of the models were obtained by various criteria of goodness of fit such as coefficients of determination (R2), Root Mean Square Error (RMSE), Akaike's Information Criterion (AIC), Bayesian Information Criterion (BIC), graphical analysis, and Chi-square test. The results indicated that RF, MCM, SF, and PF were best models for fitting weekly egg production curve due to higher values of R2 and low values of RMSE, AIC, and BIC as compare to remaining models. In case of weekly egg weight, the best values of goodness of fit criteria were showed by MMF model followed by MCM and LM model. The results indicated that these models could be conveniently used for fitting for weekly egg production and egg weight in synthetic white leghorn, respectively.


Subject(s)
Chickens , Models, Biological , Animals , Bayes Theorem , Models, Theoretical , Reproducibility of Results
17.
Autophagy ; 18(4): 944-945, 2022 04.
Article in English | MEDLINE | ID: mdl-35167411

ABSTRACT

Very little is known about the mechanisms that restrict neurotropic herpesviruses such as herpes simplex virus-1 (HSV-1) from infecting the central nervous system (CNS) and causing widespread death of neurons. Likewise, HSV-1 is thought to play a role in chronic neurodegeneration, yet a direct association has remained elusive. To address these issues, we recently showed that the selective macroautophagy/autophagy receptor OPTN (optineurin) specifically targets HSV-1 proteins VP16 and gB for degradation to prevent viral spread in the brain. OPTN deficiency alters host cytokine expression and tissue-specific immune signaling, and enhances necroptotic death of infected neurons. HSV-1-infected optn knockout mice show higher susceptibility to lethal CNS infection and the surviving animals demonstrate cognitive deficiency. Our research suggests that OPTN-mediated autophagy provides an intrinsic immune barrier against neurotropic viruses and protects the CNS from neurodegenerative stress.


Subject(s)
Herpes Simplex , Herpesviridae Infections , Herpesvirus 1, Human , Animals , Autophagy , Cell Cycle Proteins/metabolism , Herpes Simplex/metabolism , Herpesvirus 1, Human/metabolism , Macroautophagy , Membrane Transport Proteins , Mice , Mice, Knockout
18.
Heliyon ; 8(1): e08719, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35059517

ABSTRACT

The empirical affirmation in the electronics industry is that the power of chips per unit area is growing exponentially. The amount of heat generated is equal to the power; hence as power per unit area increases, so does the amount of heat generated within the chip. Thus, it necessary to mitigate the thermal problems of electronic systems. If not addressed or suppressed, thermal problems can lead to various issues including dielectric breakdown, electromigration, material creeping, unwanted chemical reactions, board warpage, drift in performance, and indirect heating. In this study, a dedicated thermal collection network (TCN) in the back end of the line area of an electronic chip was investigated. This network can help in creating a connection using a thermal through Silicon via (TTSV) to pump up the thermal energy to the heat-sink-fan assembly. Pre-empting heat from the sources could manage the thermal issues arising in chips as well as three-dimensional integrated circuit (3-D IC) structures. The finite-element method was the tool used for analysis. 31.62% of heat suction in TCNs of monolithic ICs, 11.36% in TCNs of 3-D IC structures, and 35.34% of heat suction in junctions of TTSVs compared with different approaches without the postulate used here. This procedure is expected to lead to a new path for redesigning electronic chips and 3-D IC structures.

19.
J Immunol ; 208(1): 63-73, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34880107

ABSTRACT

Very little knowledge exists on virus-specific host cell intrinsic mechanisms that prevent hyperproliferation of primary HSV type 2 (HSV-2) genital infections. In this study, we provide evidence that the Nemo-related protein, optineurin (OPTN), plays a key role in restricting HSV-2 infection both in vitro and in vivo. Contrary to previous reports regarding the proviral role of OPTN during Sendai virus infection, we demonstrate that lack of OPTN in cells causes enhanced virus production. OPTN deficiency negatively affects the host autophagy response and results in a marked reduction of CCL5 induction. OPTN knockout (OPTN-/-) mice display exacerbated genital disease and dysregulated T cell frequencies in infected tissues and lymph nodes. A human transcriptomic profile dataset provides further credence that a strong positive correlation exists between CCL5 upregulation and OPTN expression during HSV-2 genital infection. Our findings underscore a previously unknown OPTN/CCL5 nexus that restricts hyperproliferative spread of primary HSV-2 infection, which may constitute an intrinsic host defense mechanism against herpesviruses in general.


Subject(s)
Cell Cycle Proteins/metabolism , Herpes Genitalis/immunology , Herpesvirus 2, Human/physiology , Membrane Transport Proteins/metabolism , Animals , Antigens, Viral/immunology , Autophagy , Cell Cycle Proteins/genetics , Chemokine CCL5/genetics , Chemokine CCL5/metabolism , Female , Gene Knockdown Techniques , HeLa Cells , Humans , Immunity, Innate , Membrane Transport Proteins/genetics , Mice , Mice, Inbred C57BL , Mice, Knockout , Peptides/immunology , RNA, Small Interfering/genetics , Virus Replication
20.
mBio ; 12(6): e0279221, 2021 12 21.
Article in English | MEDLINE | ID: mdl-34749529

ABSTRACT

Under pathological conditions like herpes simplex virus 1 (HSV-1) infection, host-pathogen interactions lead to major reconstruction of the host protein network, which contributes to the dysregulation of signaling pathways and disease onset. Of note is the upregulation of a multifunctional host protein, heparanase (HPSE), following infection, which serves as a mediator in HSV-1 replication. In this study, we identify a novel function of HPSE and highlight it as a key regulator of ß-catenin signal transduction. The regulatory role of HPSE on the activation, nuclear translocation, and signal transduction of ß-catenin disrupts cellular homeostasis and establishes a pathogenic environment that promotes viral replication. Under normal physiological conditions, ß-catenin is bound to a group of proteins, referred to as the destruction complex, and targeted for ubiquitination and, ultimately, degradation. We show that virus-induced upregulation of HPSE leads to the activation of Akt and subsequent stabilization and activation of ß-catenin through (i) the release of ß-catenin from the destruction complex, and (ii) direct phosphorylation of ß-catenin at Ser552. This study also provides an in-depth characterization of the proviral role of ß-catenin signaling during HSV-1 replication using physiologically relevant cell lines and in vivo models of ocular infection. Furthermore, pharmacological inhibitors of this pathway generated a robust antiviral state against multiple laboratory and clinical strains of HSV-1. Collectively, our findings assign a novel regulatory role to HPSE as a driver of ß-catenin signaling in HSV-1 infection. IMPORTANCE Heparanase (HPSE) and ß-catenin have independently been implicated in regulating key pathophysiological processes, including neovascularization, angiogenesis, and inflammation; however, the relationship between the two proteins has remained elusive thus far. For that reason, characterizing this relationship is crucial and can lead to the development of novel therapeutics. For HSV-1 specifically, current antivirals are not able to abolish the virus from the host, leaving patients susceptible to episodes of viral reactivation. Identifying a host-based intervention can provide a better alternative with enhanced efficacy and sustained relief.


Subject(s)
Glucuronidase/metabolism , Herpes Simplex/enzymology , Herpesvirus 1, Human/physiology , Proto-Oncogene Proteins c-akt/metabolism , beta Catenin/metabolism , Amino Acid Motifs , Cell Line , Glucuronidase/genetics , Herpes Simplex/genetics , Herpes Simplex/metabolism , Herpes Simplex/virology , Herpesvirus 1, Human/genetics , Host-Pathogen Interactions , Humans , Phosphorylation , Proto-Oncogene Proteins c-akt/genetics , Virus Activation , Virus Replication , Wnt Signaling Pathway , beta Catenin/chemistry , beta Catenin/genetics
SELECTION OF CITATIONS
SEARCH DETAIL