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Article ; Online: Mrj is a chaperone of the Hsp40 family that regulates Orb2 oligomerization and long-term memory in Drosophila.

Desai, Meghal / Hemant / Deo, Ankita / Naik, Jagyanseni / Dhamale, Prathamesh / Kshirsagar, Avinash / Bose, Tania / Majumdar, Amitabha

PLoS biology

2024 Volume 22, Issue 4, Page(s) e3002585

Abstract: Orb2 the Drosophila homolog of cytoplasmic polyadenylation element binding (CPEB) protein forms prion-like oligomers. These oligomers consist of Orb2A and Orb2B isoforms and their formation is dependent on the oligomerization of the Orb2A isoform. ... ...

Abstract	Orb2 the Drosophila homolog of cytoplasmic polyadenylation element binding (CPEB) protein forms prion-like oligomers. These oligomers consist of Orb2A and Orb2B isoforms and their formation is dependent on the oligomerization of the Orb2A isoform. Drosophila with a mutation diminishing Orb2A's prion-like oligomerization forms long-term memory but fails to maintain it over time. Since this prion-like oligomerization of Orb2A plays a crucial role in the maintenance of memory, here, we aim to find what regulates this oligomerization. In an immunoprecipitation-based screen, we identify interactors of Orb2A in the Hsp40 and Hsp70 families of proteins. Among these, we find an Hsp40 family protein Mrj as a regulator of the conversion of Orb2A to its prion-like form. Mrj interacts with Hsp70 proteins and acts as a chaperone by interfering with the aggregation of pathogenic Huntingtin. Unlike its mammalian homolog, we find Drosophila Mrj is neither an essential gene nor causes any gross neurodevelopmental defect. We observe a loss of Mrj results in a reduction in Orb2 oligomers. Further, Mrj knockout exhibits a deficit in long-term memory and our observations suggest Mrj is needed in mushroom body neurons for the regulation of long-term memory. Our work implicates a chaperone Mrj in mechanisms of memory regulation through controlling the oligomerization of Orb2A and its association with the translating ribosomes.
MeSH term(s)	Animals ; Drosophila melanogaster/metabolism ; Drosophila melanogaster/genetics ; Drosophila Proteins/metabolism ; Drosophila Proteins/genetics ; HSP40 Heat-Shock Proteins/metabolism ; HSP40 Heat-Shock Proteins/genetics ; HSP70 Heat-Shock Proteins/metabolism ; HSP70 Heat-Shock Proteins/genetics ; Memory, Long-Term/physiology ; mRNA Cleavage and Polyadenylation Factors/metabolism ; mRNA Cleavage and Polyadenylation Factors/genetics ; Mushroom Bodies/metabolism ; Protein Multimerization ; Transcription Factors/metabolism ; Transcription Factors/genetics ; Molecular Chaperones/genetics ; Molecular Chaperones/metabolism
Chemical Substances	Drosophila Proteins ; HSP40 Heat-Shock Proteins ; HSP70 Heat-Shock Proteins ; mRNA Cleavage and Polyadenylation Factors ; Orb2 protein, Drosophila ; Transcription Factors ; mrj protein, Drosophila ; Molecular Chaperones
Language	English
Publishing date	2024-04-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2126776-5
ISSN	1545-7885 ; 1544-9173
ISSN (online)	1545-7885
ISSN	1544-9173
DOI	10.1371/journal.pbio.3002585
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Article ; Online: The expanding impact of T-regs in the skin.

Hajam, Edries Yousaf / Panikulam, Patricia / Chu, Chung-Ching / Jayaprakash, Haarshadri / Majumdar, Amitabha / Jamora, Colin

Frontiers in immunology

2022 Volume 13, Page(s) 983700

Abstract: As the interface between the body and the environment, the skin functions as the physical barrier against external pathogens and toxic agents. In addition, the skin is an immunologically active organ with a plethora of resident adaptive and innate immune ...

Abstract	As the interface between the body and the environment, the skin functions as the physical barrier against external pathogens and toxic agents. In addition, the skin is an immunologically active organ with a plethora of resident adaptive and innate immune cells, as well as effector molecules that provide another layer of protection in the form of an immune barrier. A major subpopulation of these immune cells are the Foxp3 expressing CD4 T cells or regulatory T cells (T-regs). The canonical function of T-regs is to keep other immune cells in check during homeostasis or to dissipate a robust inflammatory response following pathogen clearance or wound healing. Interestingly, recent data has uncovered unconventional roles that vary between different tissues and we will highlight the emerging non-lymphoid functions of cutaneous T-regs. In light of the novel functions of other immune cells that are routinely being discovered in the skin, their regulation by T-regs implies that T-regs have executive control over a broad swath of biological activities in both homeostasis and disease. The blossoming list of non-inflammatory functions, whether direct or indirect, suggests that the role of T-regs in a regenerative organ such as the skin will be a field ripe for discovery for decades to come.
MeSH term(s)	Forkhead Transcription Factors ; Homeostasis ; Skin ; T-Lymphocytes, Regulatory
Chemical Substances	Forkhead Transcription Factors
Language	English
Publishing date	2022-09-15
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.983700
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Article ; Online: Small molecules enhance the potency of natural antimicrobial peptides.

Losasso, Valeria / Agarwal, Khushbu / Waskar, Morris / Majumdar, Amitabha / Crain, Jason / Winn, Martyn / Hoptroff, Michael

Biophysical journal

2021 Volume 121, Issue 3, Page(s) 491–501

Abstract: The skin-associated microbiome plays an important role in general well-being and in a variety of treatable skin conditions. In this regard, endogenous antimicrobial peptides have both a direct and indirect role in determining the composition of the ... ...

Abstract	The skin-associated microbiome plays an important role in general well-being and in a variety of treatable skin conditions. In this regard, endogenous antimicrobial peptides have both a direct and indirect role in determining the composition of the microbiota. We demonstrate here that certain small molecular species can amplify the antimicrobial potency of naturally occurring antimicrobial peptides. In this study, we have used niacinamide, a form of vitamin B3 naturally found in foods and widely used in cosmetic skincare products, and two of its structural analogs, to investigate their cooperativity with the human antimicrobial peptide LL37 on the bacterium Staphylococcus aureus. We observed a clear synergistic effect of niacinamide and, to some extent, N-methylnicotinamide, whereas isonicotinamide showed no significant cooperativity with LL37. Adaptively biased molecular dynamics simulations using simplified model membrane substrates and single peptides revealed that these molecules partition into the headgroup region of an anionic bilayer used to mimic the bacterial membrane. The simulated effects on the physical properties of the simulated model membrane are well correlated with experimental activity observed in real biological assays despite the simplicity of the model. In contrast, these molecules have little effect on zwitterionic bilayers that mimic a mammalian membrane. We conclude that niacinamide and N-methylnicotinamide can therefore potentiate the activity of host peptides by modulating the physical properties of the bacterial membrane, and to a lesser extent through direct interactions with the peptide. The level of cooperativity is strongly dependent on the detailed chemistry of the additive, suggesting an opportunity to fine-tune the behavior of host peptides.
MeSH term(s)	Animals ; Anti-Infective Agents/chemistry ; Anti-Infective Agents/pharmacology ; Antimicrobial Peptides ; Humans ; Lipid Bilayers/chemistry ; Mammals ; Niacinamide ; Peptides/chemistry
Chemical Substances	Anti-Infective Agents ; Antimicrobial Peptides ; Lipid Bilayers ; Peptides ; Niacinamide (25X51I8RD4)
Language	English
Publishing date	2021-12-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218078-9
ISSN	1542-0086 ; 0006-3495
ISSN (online)	1542-0086
ISSN	0006-3495
DOI	10.1016/j.bpj.2021.12.029
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Zs.A 235: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Glycerol fermentation by skin bacteria generates lactic acid and upregulates the expression levels of genes associated with the skin barrier function.

Salgaonkar, Neha / Kadamkode, Vinitha / Kumaran, Srikala / Mallemala, Prathyusha / Christy, Ernest / Appavoo, Shanthi / Majumdar, Amitabha / Mitra, Rupak / Dasgupta, Anindya

Experimental dermatology

2022 Volume 31, Issue 9, Page(s) 1364–1372

Abstract: Commensal bacteria play a major role in multiple skin functions by providing the first layer of defense against pathogens and maintaining the skin barrier. Staphylococcus epidermidis is one of the most common skin commensals. In this study, we showed ... ...

Abstract	Commensal bacteria play a major role in multiple skin functions by providing the first layer of defense against pathogens and maintaining the skin barrier. Staphylococcus epidermidis is one of the most common skin commensals. In this study, we showed that S. epidermidis ferments glycerol and uses it as a nutrient, while producing short-chain and organic fatty acids, with the most notable being lactic acid. Lactic acid is an alpha-hydroxy acid that inhibits the growth of pathogenic bacteria, without any negative effect on the commensal bacteria itself. Using in vivo experiments, we validated our in vitro results, showing that the skin microbiome is also capable of doing this. Finally, using 2D and 3D skin culture models, we showed that the fermentation of glycerol, mainly lactic acid, as determined by analytical methods, upregulates the expression levels of several key genes that are associated with the barrier properties of the skin. While the hydration effect of glycerol on the skin is well known, our study shows the overall benefits of glycerol on the skin microbiome, while revealing an alternate mode of action of glycerol for multiple skin benefits.
MeSH term(s)	Fermentation ; Glycerol/pharmacology ; Lactic Acid/metabolism ; Skin/metabolism ; Staphylococcus epidermidis/physiology
Chemical Substances	Lactic Acid (33X04XA5AT) ; Glycerol (PDC6A3C0OX)
Language	English
Publishing date	2022-05-25
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	1130936-2
ISSN	1600-0625 ; 0906-6705
ISSN (online)	1600-0625
ISSN	0906-6705
DOI	10.1111/exd.14604
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Zs.A 3508: Show issues

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Article: A cost-effective and efficient approach for generating and assembling reagents for conducting real-time PCR [Erratum: March 2022, v.47(1), p.5]

Mote, Ridim D / Laxmikant, V Shinde / Singh, Surya Bansi / Tiwari, Mahak / Singh, Hemant / Srivastava, Juhi / Tripathi, Vidisha / Seshadri, Vasudevan / Majumdar, Amitabha / Subramanyam, Deepa

Journal of biosciences. 2021 Dec., v. 46, no. 4

2021

Abstract: Real-time PCR is a widely used technique for quantification of gene expression. However, commercially available kits for real-time PCR are very expensive. The ongoing coronavirus pandemic has severely hampered the economy in a number of developing ... ...

Abstract	Real-time PCR is a widely used technique for quantification of gene expression. However, commercially available kits for real-time PCR are very expensive. The ongoing coronavirus pandemic has severely hampered the economy in a number of developing countries, resulting in a reduction in available research funding. The fallout of this will result in limiting educational institutes and small enterprises from using cutting edge biological techniques such as real-time PCR. Here, we report a cost-effective approach for preparing and assembling cDNA synthesis and real-time PCR mastermixes with similar efficiencies as commercially available kits. Our results thus demonstrate an alternative to commercially available kits.
Keywords	cost effectiveness ; gene expression ; pandemic ; quantitative polymerase chain reaction
Language	English
Dates of publication	2021-12
Size	p. 109.
Publishing place	Springer India
Document type	Article
ZDB-ID	756157-x
ISSN	0973-7138 ; 0250-5991
ISSN (online)	0973-7138
ISSN	0250-5991
DOI	10.1007/s12038-021-00231-w
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Article ; Online: Uterine arteriovenous malformation: A rising cause of postpartum haemorrhage?

Mosedale, Thomas E / Martin, Gillian / Majumdar, Amitabha

Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology

2016 Volume 36, Issue 5, Page(s) 687–689

MeSH term(s)	Adult ; Arteriovenous Malformations/complications ; Female ; Humans ; Postpartum Hemorrhage/etiology ; Pregnancy ; Uterine Artery/abnormalities
Language	English
Publishing date	2016-07
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	604639-3
ISSN	1364-6893 ; 0144-3615
ISSN (online)	1364-6893
ISSN	0144-3615
DOI	10.3109/01443615.2016.1148682
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Zs.B 2461: Show issues

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Article ; Online: Niacinamide enhances cathelicidin mediated SARS-CoV-2 membrane disruption.

Bhatt, Tanay / Dam, Binita / Khedkar, Sneha Uday / Lall, Sahil / Pandey, Subhashini / Kataria, Sunny / Ajnabi, Johan / Gulzar, Shah-E-Jahan / Dias, Paul M / Waskar, Morris / Raut, Janhavi / Sundaramurthy, Varadharajan / Vemula, Praveen Kumar / Ghatlia, Naresh / Majumdar, Amitabha / Jamora, Colin

Frontiers in immunology

2023 Volume 14, Page(s) 1255478

Abstract: The continual emergence of SARS-CoV-2 variants threatens to compromise the effectiveness of worldwide vaccination programs, and highlights the need for complementary strategies for a sustainable containment plan. An effective approach is to mobilize the ... ...

Abstract	The continual emergence of SARS-CoV-2 variants threatens to compromise the effectiveness of worldwide vaccination programs, and highlights the need for complementary strategies for a sustainable containment plan. An effective approach is to mobilize the body's own antimicrobial peptides (AMPs), to combat SARS-CoV-2 infection and propagation. We have found that human cathelicidin (LL37), an AMP found at epithelial barriers as well as in various bodily fluids, has the capacity to neutralise multiple strains of SARS-CoV-2. Biophysical and computational studies indicate that LL37's mechanism of action is through the disruption of the viral membrane. This antiviral activity of LL37 is enhanced by the hydrotropic action of niacinamide, which may increase the bioavailability of the AMP. Interestingly, we observed an inverse correlation between LL37 levels and disease severity of COVID-19 positive patients, suggesting enhancement of AMP response as a potential therapeutic avenue to mitigate disease severity. The combination of niacinamide and LL37 is a potent antiviral formulation that targets viral membranes of various variants and can be an effective strategy to overcome vaccine escape.
MeSH term(s)	Humans ; Cathelicidins/pharmacology ; SARS-CoV-2 ; Antimicrobial Cationic Peptides/pharmacology ; Niacinamide ; COVID-19 ; Antiviral Agents
Chemical Substances	Cathelicidins ; Antimicrobial Cationic Peptides ; Niacinamide (25X51I8RD4) ; Antiviral Agents
Language	English
Publishing date	2023-11-08
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1255478
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Article ; Online: Correction to: A cost-effective and efficient approach for generating and assembling reagents for conducting real-time PCR.

Mote, Ridim D / Laxmikant, Shinde / Singh, Surya Bansi / Tiwari, Mahak / Singh, Hemant / Srivastava, Juhi / Tripathi, Vidisha / Seshadri, Vasudevan / Majumdar, Amitabha / Subramanyam, Deepa

Journal of biosciences

2022 Volume 47

Abstract: In Volume 46 of the Journal of Biosciences, in the article titled 'A cost-effective and efficient approach for generating and assembling reagents for conducting real-time PCR' by Ridim D Mote, V Shinde Laxmikant, Surya Bansi Singh, Mahak Tiwari, Hemant ... ...

Abstract	In Volume 46 of the Journal of Biosciences, in the article titled 'A cost-effective and efficient approach for generating and assembling reagents for conducting real-time PCR' by Ridim D Mote, V Shinde Laxmikant, Surya Bansi Singh, Mahak Tiwari, Hemant Singh, Juhi Srivastava, Vidisha Tripathi,Vasudevan Seshadri, Amitabha Majumdar and Deepa Subramanyam, published on 27 November 2021 (https://doi.org/10.1007/s12038-021- 00231-w), the second author's name was incorrectly set as V Shinde Laxmikant. The correct name should read as Shinde Laxmikant V.
Language	English
Publishing date	2022-01-29
Publishing country	India
Document type	Journal Article
ZDB-ID	756157-x
ISSN	0973-7138 ; 0250-5991
ISSN (online)	0973-7138
ISSN	0250-5991
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Article: A role of cellular translation regulation associated with toxic Huntingtin protein

Joag, Hiranmay / Ghatpande, Vighnesh / Desai, Meghal / Sarkar, Maitheli / Raina, Anshu / Shinde, Mrunalini / Chitale, Ruta / Deo, Ankita / Bose, Tania / Majumdar, Amitabha

Cellular and molecular life sciences. 2020 Sept., v. 77, no. 18

2020

Abstract: Huntington’s disease (HD) is a severe neurodegenerative disorder caused by poly Q repeat expansion in the Huntingtin (Htt) gene. While the Htt amyloid aggregates are known to affect many cellular processes, their role in translation has not been ... ...

Abstract	Huntington’s disease (HD) is a severe neurodegenerative disorder caused by poly Q repeat expansion in the Huntingtin (Htt) gene. While the Htt amyloid aggregates are known to affect many cellular processes, their role in translation has not been addressed. Here we report that pathogenic Htt expression causes a protein synthesis deficit in cells. We find a functional prion-like protein, the translation regulator Orb2, to be sequestered by Htt aggregates in cells. Co-expression of Orb2 can partially rescue the lethality associated with poly Q expanded Htt. These findings can be relevant for HD as human homologs of Orb2 are also sequestered by pathogenic Htt aggregates. Our work suggests that translation dysfunction is one of the contributors to the pathogenesis of HD and new therapies targeting protein synthesis pathways might help to alleviate disease symptoms.
Keywords	amyloid ; death ; genes ; humans ; neurodegenerative diseases ; pathogenesis ; protein synthesis ; toxicity
Language	English
Dates of publication	2020-09
Size	p. 3657-3670.
Publishing place	Springer International Publishing
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-019-03392-y
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Article ; Online: Correction: Keratinocyte differentiation promotes ER stress-dependent lysosome biogenesis.

Mahanty, Sarmistha / Dakappa, Shruthi Shirur / Shariff, Rezwan / Patel, Saloni / Swamy, Mruthyunjaya Mathapathi / Majumdar, Amitabha / Setty, Subba Rao Gangi

Cell death & disease

2019 Volume 10, Issue 10, Page(s) 740

Abstract: Following publication of this article, the authors realized there was an error in Figure 2b that needed correction. The TFEB panel of Figure 2b (total lysate) appears to be the same as the TFEB panel of Figure 2e (cytosolic fraction); the TFE3 panels of ... ...

Abstract	Following publication of this article, the authors realized there was an error in Figure 2b that needed correction. The TFEB panel of Figure 2b (total lysate) appears to be the same as the TFEB panel of Figure 2e (cytosolic fraction); the TFE3 panels of Figure 2b (total lysate) appear to be the same as the TFE3 panels of Figure 2e (cytosolic fraction) which happened during image assembly.This error did not impact the scientific conclusions of the article.
Language	English
Publishing date	2019-10-03
Publishing country	England
Document type	Published Erratum
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-019-1981-7
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