Biology subjects

Borah, S.

Publications and source records attributed to Borah, S..

7 recordsLinked to original sources

bioRxiv2026

Increased expression of Cd74 and MHC II genes by aortic macrophages links atherosclerosis with aging in mice

Atherosclerosis is a chronic inflammatory condition of the arteries leading to myocardial infarction, ischemic stroke and peripheral arterial diseases. Atherosclerotic plaques, which obstruct blood flow contain functionally diverse macrophage populations including pro-atherogenic and atheroprotective subsets. Aging is a major risk factor of atherosclerosis, but the mechanism underlying aging associated risk of atherosclerosis is unclear. Here, using integrated single-cell RNA sequencing data analysis, we demonstrate that specific monocyte and macrophage subsets are enriched in atherosclerotic plaques and the aging aorta of mice. We also show that Cd74 and MHCII genes such as H2-Aa, H2-Ab1, H2-Eb1, and H2-DMb1 are consistently upregulated in the monocytes and macrophages from atherosclerotic plaques, the aging aorta, and the aging bone marrow of mice. Our experimental data also show increased expression of CD74 surface protein by aortic macrophages and bone marrow monocytes from aged mice. In addition, we show increased CD74 expression by RAW264.7 mouse macrophages and THP1 human monocytes following ox-LDL stimulation in vitro. Finally, we demonstrate that monocytes from aged mice adhere more to aortic endothelial cells in co-cultures. Thus, increased monocyte adhesion to endothelial cells may explain the enhanced proportion of specific monocyte and macrophage subsets in the aging aorta, inducing a pre-atherosclerotic condition.

immunology↗

bioRxiv2025

Dynamic cytokine interplay governing implantation and immune tolerance in pregnant pigs

Embryo implantation in pigs represents a complex immunological and biochemical interaction between the developing conceptus and the maternal endometrium. The present study investigated temporal changes in key cytokines associated with successful implantation and early pregnancy in pigs. Twelve healthy sows (HDK75: 75% Hampshire x 25% local) were divided equally into pregnant and non-pregnant groups. Blood samples were collected from day 0 to day 42 post-insemination at weekly intervals, and plasma concentrations of cytokines--IFN-{gamma}, IFN-{beta}, IL-1, IL-1{beta}, IL-1RA, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, and TNF- were quantified using ELISA.A significant (p < 0.05) progressive increase was observed in all cytokines in pregnant pigs, indicating active immunomodulation during early gestation. IFN-{gamma}, IL-1{beta}, and TNF- showed sharp elevations, reflecting their roles in endometrial receptivity, inflammation, and trophoblast invasion. Concurrently, IL-1RA, IL-4 and IL-10 exhibited marked increases, suggesting an anti-inflammatory shift crucial for maternal-fetal immune tolerance. The coordinated rise of IL-6, IL-8, IL-12, and IL-18 further indicated involvement in vascular remodeling and angiogenesis essential for placental development. In contrast, non-pregnant pigs displayed stable cytokine levels across all sampling points, confirming the absence of immune activation or inflammatory stimuli. These findings demonstrate that successful implantation in pigs is governed by a dynamic cytokine network balancing pro- and anti-inflammatory mediators. The interplay among these cytokines ensures immune tolerance, endometrial remodeling and vascular adaptation necessary for embryo attachment and maintenance of early pregnancy. The study highlights cytokine profiling as a potential biomarker approach for monitoring reproductive status in pigs.

immunology↗

bioRxiv2024

Effect of zinc supplementation on certain serum biochemical parameters in growing pigs

Twenty-four healthy and uniform crossbred (Hampshire x Assam Local) pigs, 4 months of age, were selected to study the effect of 500 ppm Zn supplementation on certain serum biochemical parameters for a period of four months. The animals were divided into three groups (n=8/group): group C (basal diet), group T1 (basal diet + 100 ppm Zn + calcium carbonate @ 1.5% DM) and group T2 (basal diet + 500 ppm Zn). Serum samples were collected at 15-day intervals and analysed for serum Zn, copper, total serum protein, albumin, globulin, and glucose cholesterol. The serum Zn concentration in the T1 group decreased significantly (P<0.01) from day 30 until day 120 of treatment, whereas in the T2 group, the level increased significantly (P<0.01) from day 15 onwards. The serum copper concentration did not change groups. The total protein concentration in the serum showed a significant (P<0.01) increasing trend in the T2 group from day 45 of treatment, and a significant (P<0.01) decreasing trend was observed in the T1 group compared to the C group. The serum globulin concentration decreased significantly (P< 0.05) in the T1 group compared with the C and T2 groups during the treatment period. An increasing trend in glucose and cholesterol levels was recorded at T2 during the treatment period. However, decrease, (P<0.01) in glucose and cholesterol levels was recorded in the T1 group from day 30 to day 120 of treatment. The haemoglobin concentration showed a significant (p<0.01) decreasing trend in the T1 group from day 45 onwards.

physiology↗

bioRxiv2020

Heh2/Man1 may be an evolutionarily conserved sensor of NPC assembly state

Integral membrane proteins of the Lap2-emerin-MAN1 (LEM) family have emerged as important components of the inner nuclear membrane (INM) required for the functional and physical integrity of the nuclear envelope. However, like many INM proteins, there is limited understanding of the biochemical interaction networks that enable LEM protein function. Here, we show that Heh2/Man1 can be affinity purified with major scaffold components of the nuclear pore complex (NPC), specifically the inner ring complex, in evolutionarily distant yeasts. Interactions between Heh2 and nucleoporins is mediated by its C-terminal winged-helix (WH) domain and are distinct from interactions required for INM targeting. Disrupting interactions between Heh2 and the NPC leads to NPC clustering. Interestingly, Heh2s association with NPCs can also be broken by knocking out Nup133, a component of the outer ring that does not physically interact with Heh2. Thus, Heh2s association with NPCs depends on the structural integrity of both major NPC scaffold complexes. We propose a model in which Heh2 acts as a sensor of NPC assembly state, which may be important for NPC quality control mechanisms and the segregation of NPCs during cell division.

cell biology↗

bioRxiv2020

Direct PA-binding by Chm7 is required for nuclear envelope surveillance at herniations

Mechanisms that control nuclear membrane remodeling are essential to maintain the integrity of the nucleus but remain to be fully defined. Here, we identify a phosphatidic acid (PA)-binding activity in the nuclear envelope-specific ESCRT, Chm7, in budding yeast. PA-binding is mediated through a conserved hydrophobic stretch of amino acids, which confers specific binding to the inner nuclear membrane (INM). This INM-binding is independent but nonetheless required for interaction with the LAP2-emerin-MAN1 (LEM) domain protein, Heh1 (LEM2). Consistent with the functional importance of PA-binding, mutation of this region inhibits recruitment of Chm7 to the INM and abolishes Chm7 function in the context of nuclear envelope herniations or "blebs" that form during defective nuclear pore complex (NPC) biogenesis. In fact, we show that PA accumulates at nuclear envelope herniations. We suggest that local control of PA metabolism is important for ensuring productive nuclear envelope remodeling and that its dysregulation may contribute to pathologies associated with defective NPC assembly.

cell biology↗

bioRxiv2019

An ESCRT-LEM domain inner nuclear membrane protein surveillance system is poised to directly monitor the integrity of the nuclear envelope barrier and nuclear transport system

The integrity of the nuclear envelope membranes coupled to the diffusion barrier and selective transport properties of nuclear pore complexes (NPCs) are a prerequisite for the robust segregation of nucleoplasm and cytoplasm. Recent work supports that mechanical membrane disruption or perturbation to NPC assembly can trigger an ESCRT-dependent surveillance system that seals nuclear envelope pores: how these pores are sensed and sealed remains to be fully defined. Here, we show that the principal components of the nuclear envelope surveillance system in yeast, which includes the ESCRT Chm7 and the integral inner nuclear membrane (INM) protein Heh1, are spatially segregated by the nuclear transport system. Specifically, at steady state Chm7 is actively restricted from the nucleus by Crm1/Xpo1. Consistent with the idea that it is the exposure of the INM that triggers surveillance, the expression of a transmembrane anchor and the winged helix domain of Heh1 is sufficient to recruit and activate Chm7 at a membrane interface. Correlative light electron tomography under conditions of Chm7 hyper-activation further show the formation of an elaborate network of fenestrated sheets at the INM and suggest ER-membrane delivery at sites of nuclear envelope herniation. Our data point to a model in which exposure of Chm7 to Heh1, driven by any perturbation in the nuclear envelope barrier would lead to local nuclear envelope remodeling to promote membrane sealing. Our findings have implications for disease mechanisms associated with defects in NPC assembly and nuclear envelope integrity.

cell biology↗

bioRxiv2018

Expression of TorsinA in a heterologous yeast system reveals interactions with conserved lumenal domains of LINC and nuclear pore complexes

DYT1 dystonia is caused by an in-frame deletion of a glutamic acid codon in the gene encoding the AAA+ ATPase TorsinA. TorsinA localizes within the lumen of the nuclear envelope/ER and binds to a membrane-spanning co-factor, LAP1 or LULL1, to form an ATPase; the substrate(s) of TorsinA remain ill defined. Here we use budding yeast, which lack Torsins, to interrogate TorsinA function. We show that TorsinA accumulates at nuclear envelope embedded spindle pole bodies (SPBs) in a way that requires its oligomerization and the conserved SUN-domain protein, Mps3. TorsinA is released from SPBs upon expression of LAP1 and stabilized by LAP1 mutants incapable of stimulating TorsinA ATPase activity, suggesting the recapitulation of a TorsinA-substrate cycle. While the expression of TorsinA or TorsinA-{Delta}E impacts the fitness of strains expressing mps3 alleles, a genetic interaction with a conserved component of the nuclear pore complex, Pom152, is specific for TorsinA. This specificity is mirrored by a physical interaction between Pom152 and TorsinA, but not TorsinA-{Delta}E. These data suggest that TorsinA-nucleoporin interactions would be abrogated by TorsinA-{Delta}E, providing new experimental avenues to interrogate the molecular basis behind nuclear envelope herniations seen in cells lacking TorsinA function.

cell biology↗