Lamin A K97E leads to NF-κB-mediated dysfunction of inflammatory responses in dilated cardiomyopathy.

BACKGROUND INFORMATION: Lamins are type V intermediate filament proteins underlying the inner nuclear membrane which provide structural rigidity to the nucleus, tether the chromosomes, maintain nuclear homeostasis, and remain dynamically associated with developmentally regulated regions of the genome. A large number of mutations particularly in the LMNA gene encoding lamin A/C results in a wide array of human diseases, collectively termed as laminopathies. Dilated Cardiomyopathy (DCM) is one such laminopathic cardiovascular disease which is associated with systolic dysfunction of left or both ventricles leading to cardiac arrhythmia which ultimately culminates into myocardial infarction. RESULTS: In this work, we have unraveled the epigenetic landscape to address the regulation of gene expression in mouse myoblast cell line in the context of the missense mutation LMNA 289A

High Sensitivity and High Throughput Magnetic Flow CMOS Cytometers with 2D Oscillator Array and Inter-Sensor Spectrogram Cross-correlation.

In the paper, we present an integrated flow cytometer with a 2D array of magnetic sensors based on dual-frequency oscillators in a 65-nm CMOS process, with the chip packaged with microfluidic controls. The sensor architecture and the presented array signal processing allows uninhibited flow of the sample for high throughput without the need for hydrodynamic focusing to a single sensor. To overcome the challenge of sensitivity and specificity that comes as a trade off with high throughout, we perform two levels of signal processing. First, utilizing the fact that a magnetically tagged cell is expected to excite sequentially an array of sensors in a time-delayed fashion, we perform inter-site cross-correlation of the sensor spectrograms that allows us to suppress the probability of false detection drastically, allowing theoretical sensitivity reaching towards sub-ppM levels that is needed for rare cell or circulating tumor cell detection. In addition, we implement two distinct methods to suppress correlated low frequency drifts of singular sensors-one with an on-chip sensor reference and one that utilizes the frequency dependence of the susceptibility of super-paramagnetic magnetic beads that we deploy as tags. We demonstrate these techniques on a 7×7 sensor array in 65 nm CMOS technology packaged with microfluidics with magnetically tagged dielectric particles and cultu lymphoma cancer cells.

Demographic and economic correlates of health security in West Sumatra province - Indonesia.

OBJECTIVES: Access to health insurances could indicate the degree of health security among communities. Indonesia made a commitment to attain universal health insurance coverage by the end of 2019. However, until today it has not reached the goal of 100% coverage. Therefore, there is a need to portray the demographic and economic correlates of health insurance coverage in an area to improve health security achievement. METHODS: This secondary analysis was based on the 2017 Indonesian national socio-economic survey conducted in the West Sumatra province. Multivariable models using logistic regression were used to estimate the odds ratios (OR) for being uninsured. RESULTS: The results showed that health security, in terms of insurance coverage, was influenced by demographic and economic factors. Young and middle-aged individuals were more likely to be uninsured than older ones (OR = 1.49 and OR = 1.21, respectively). People from a lower educated family, or with lower consumption per capita have higher risk of being uninsured (OR = 3.00 and OR = 1.26, respectively). CONCLUSION: Insurance coverage was influenced by demographic and economic factors. Policymakers should consider demographic and economic factors related to the implementation of universal health coverage. Campaign about the importance of universal health coverage should reach all citizens.

Development of geographic inequality in dental caries and its association with socioeconomic factors over an 18-year period in Denmark.

BACKGROUND: Few studies have examined the development of geographic and socioeconomic inequalities in caries over time or have simultaneously assessed individual-level socioeconomic position (SEP) and neighborhood-level factors as a multi-layered phenomenon influencing caries inequalities. This study examined (i) the trends in geographic inequalities in caries among adolescents in Denmark and (ii) how the association between SEP and caries has progressed over time, when accounting for individual and neighborhood-level confounding factors. METHODS: This nationwide repeated cross-sectional study included 15-year-olds in Denmark from 1995, 2003, and 2013 (n = 149,808). The outcome was caries experience (measured by the decayed, missing, and filled tooth surfaces [DMFS] index). The exposure of interest was SEP, indicated by the previous year's parental education, occupational social class, and (equivalized) disposable household income. Covariates included individual-level factors (immigration status, country of origin, number of children and persons in the family, and household type) and neighborhood (residence municipality)-level factors (Gini index; proportion of unemployed, low-educated, and unmarried/non-cohabiting individuals; proportion of single-parent households and households with overcrowding). Data sources included the Danish national dental and administrative social registers and Statistics Denmark's statistics database (StatBank). Data were analyzed using spatial and spatiotemporal modelling utilizing zero-inflated negative binomial regressions and integrated nested Laplace approximations for Bayesian parametric inference. Observed caries experience geo-maps of the Danish municipalities for 1995, 2003, and 2013 were created. RESULTS: Between 1995 and 2013, caries prevalence in the 15-year-olds declined sharply (1995, 71%; 2013, 45%). Caries experience declined in nearly all socioeconomic subgroups and municipalities. However, geographic inequalities persisted with higher caries levels largely concentrated in the relatively deprived areas of Denmark. Increasing relative socioeconomic inequalities in caries over time were observed with significant graded associations between SEP and caries despite adjustment for the various individual and neighborhood-level covariates and the effect of assessment year (e.g., 15-year-olds with parents having basic education had 1.91-fold [95% CI: 1.86-1.95] higher caries experience than those having parents with high education). CONCLUSIONS: Reducing these enduring inequalities will likely require additional resources and targeted supportive and preventive measures for adolescents from lower SEP backgrounds and those residing in municipalities with higher caries prevalence.

Doing science together: Gaining momentum from long-term explorative university-industry research programs.

'Doing science together' collaborations are a more intense form of university-industry interactions and are characterized by a mutual involvement and active participation of academic and company scientists in scientific research. Here, we examine the successful approach that AstraZeneca and its internationally renowned academic partners, Karolinska Institutet and Uppsala University, implemented to fully unlock the potential of all parties in long-term, explorative, truly collaborative research programs. The underlying premises of these successful research programs are three collaborative governance mechanisms (3MCs) that are required that leverage the strengths of each organization: mutual collaboration; mutually beneficial science; and a mutual governance model with senior management involvement.

An Ingestible Pill With CMOS Fluorescence Sensor Array, Bi-Directional Wireless Interface and Packaged Optics for in-Vivo Bio-Molecular Sensing.

The article presents for the first time a pill-based ingestible electronics with CMOS integrated multiplexed fluorescence bio-molecular sensor arrays, bi-directional wireless communication and packaged optics in a FDA-approved capsule for in-vivo bio-molecular sensing. The silicon chip integrates both the sensor array, and the ultra-low-power (ULP) wireless system that allows offloading sensor computing to an external base station that can reconfigure the sensor measurement time, and its dynamic range, allowing optimized high sensitivity measurement under low power consumption. The integrated receiver achieves -59 dBm receiver sensitivity dissipating 121 µW of power. The integrated transmitter operates in a dual mode FSK/OOK delivering -15 dBm of power. The 15-pixel fluorescence sensor array follows an electronic-optic co-design methodology and integrates the nano-optical filters with integrated sub-wavelength metal layers that achieves high extinction ratio (39 dB), thereby eliminating the need for bulky external optical filters. The chip integrates photo-detection circuitry and on-chip 10-bit digitation, and achieves measured sensitivity of 1.6 attomoles of fluorescence labels on surface, and between 100 pM to 1 nM of target DNA detection limit per pixel. The complete package includes a CMOS fluorescent sensor chip with integrated filter, a prototyped UV LED and optical waveguide, functionalized bioslip, off-chip power management and Tx/Rx antenna that fits in a standard FDA approved capsule size 000.

Elevated Levels of Lamin A Promote HR and NHEJ-Mediated Repair Mechanisms in High-Grade Ovarian Serous Carcinoma Cell Line.

Extensive research for the last two decades has significantly contributed to understanding the roles of lamins in the maintenance of nuclear architecture and genome organization which is drastically modified in neoplasia. It must be emphasized that alteration in lamin A/C expression and distribution is a consistent event during tumorigenesis of almost all tissues of human bodies. One of the important signatures of a cancer cell is its inability to repair DNA damage which befalls several genomic events that transform the cells to be sensitive to chemotherapeutic agents. This genomic and chromosomal instability is the most common feature found in cases of high-grade ovarian serous carcinoma. Here, we report elevated levels of lamins in OVCAR3 cells (high-grade ovarian serous carcinoma cell line) in comparison to IOSE (immortalised ovarian surface epithelial cells) and, consequently, altered damage repair machinery in OVCAR3. We have analysed the changes in global gene expression as a sequel to DNA damage induced by etoposide in ovarian carcinoma where lamin A is particularly elevated in expression and reported some differentially expressed genes associated with pathways conferring cellular proliferation and chemoresistance. We hereby establish the role of elevated lamin A in neoplastic transformation in the context of high-grade ovarian serous cancer through a combination of HR and NHEJ mechanisms.

Slower diffusion and anomalous association of R453W lamin A protein alter nuclear architecture in AD-EDMD.

Lamins maintain the shape and rigidity of the nucleus in the form of a proteinaceous scaffold underneath the inner nuclear membrane (INM) and provide anchorage to chromatin and other nuclear proteins. Mutations in the human LMNA gene encoding lamin A/C cause about 16 different diseases with distinct phenotypes collectively termed as laminopathies which affect primarily the muscle tissues as well as adipose tissues, neuromuscular junctions and multiple other organs in progeroid syndromes. Lamins contain several domains of which Ig-fold is one of the well characterized and structured domains that harbours many mutations leading to deleterious interactions with other nuclear proteins. In this work, we have elucidated the effects of 3 such mutations namely R453W, W498C and W498R on the dynamics and flexibility of the Ig-fold domain and the consequent effect on the assembly into lamina by live cell imaging, fluorescence correlation spectroscopy (FCS) and molecular dynamics (MD) simulations. From our simulation studies, we concluded that R453W exhibits the highest fluctuation at the residues 475 and 525 in the Ig fold domain compared to the wild type and other mutants. This resulted in pronounced random self-association which could be corroborated by lower diffusivity values obtained from FCS. This is the first report where such an alteration in the full length has been documented by gross changes in diffusional properties as a sequel to a mutation in the Ig fold domain.

A Fully Integrated CMOS-controlled Scalable Microfluidics and Pneumatic-free Cell Actuation and Cytometry Sensing Device.

Moore's law has enabled massive scaling of complex computing and sensing systems in modern-day chip-scale architectures allowing extremely high yield and system complexity at very low-cost. Exploiting such Moore's law, we explore silicon-based integrated circuits and chip-scale systems to interface with biological fluids to manipulate, sense, and detect cells in real-time for an end-to-end low cost, miniaturized, and high sensitivity point-of-care diagnostics platform. Elimi-nating the need for complex, expensive, large and bulky syringe pumps and optical-based cytometers, the proposed system allows pneumatic-free AC electro-osmosis bulk fluid driving capabilities controlled by the CMOS chip, and integrated dielectrophoretic cell actuation with 2µm focusing accuracy, impedance spectroscopy sensing, and separation capabilities. The paper presents, for the first-time, a CMOS-driven cellular sensing platform for microfluidics that can be translated to a wide range of biomedical applications.

Origami Microwave Imaging Array: Metasurface Tiles on a Shape-Morphing Surface for Reconfigurable Computational Imaging.

Origami is the art of paper folding that allows a single flat piece of paper to assume different 3D shapes depending on the fold patterns and the sequence of folding. Using the principles of origami along with computation imaging technique the authors demonstrate a versatile shape-morphing microwave imaging array with reconfigurable field-of-view and scene-adaptive imaging capability. Microwave/millimeter-wave based array imaging systems are expected to be the workhorse for sensory perception of future autonomous intelligent systems. The imaging capability of a planar array-based systems operating in complex scattering conditions have limited field-of-view and lack the ability to adaptively reconfigure resolution. To overcome this, here, deviations from planarity and isometry are allowed, and a shape-morphing computational imaging system is demonstrated. Implemented on a reconfigurable Waterbomb origami surface with 22 active metasurface panels that radiate near-orthogonal modes across 17-27 GHz, capability to image complex 3D objects in full details minimizing the effects of specular reflections in diffraction-limited sparse imaging with scene adaptability, reconfigurable cross-range resolution, and field-of-view is demonstrated. Such electromagnetic origami surfaces, through simultaneous surface shape-morphing ability (potentially with shape-shifting electronic materials) and electromagnetic field programmability, opens up new avenues for intelligent and robust sensing and imaging systems for a wide range of applications.

Lamin A and telomere maintenance in aging: Two to Tango.

Lamin proteins which constitute the nuclear lamina in almost all higher eukaryotes, are mainly of two types A & B encoded by LMNA and LMNB1/B2 genes respectively. While lamin A remains the principal product of LMNA gene, variants like lamin C, C2 and A∆10 are also formed as alternate splice products. Role of lamin A in aging has been highlighted in recent times due to its association with progeroid or premature aging syndromes which is classified as a type of laminopathy. Progeria caused by accelerated accumulation of lamin A Δ50 or progerin occurs due to a mutation in this LMNA gene leading to defects in post translational modification of lamin A. One of the most common and severe symptoms of progeroid laminopathy is accelerated cellular senescence or aging along with bone resorption, muscle weakness, lipodystrophy and cardiovascular disorders. On the other hand, progerin accumulation and telomere dysfunction merge as common traits in the process of chronological aging. Two major hallmarks of physiological aging in humans include loss of genomic integrity and telomere attrition which can result from defective laminar organization leading to deformed nuclear architecture and culminates into replicative senescence. This also adversely affects epigenetic landscape, mitochondrial dysfunction and several signalling pathways like DNA repair, mTOR, MAPK, TGFß. In this review, we discuss the telomere-lamina interplay in the context of physiological aging and progeria.

Proprotein convertase PCSK9 affects expression of key surface proteins in human pancreatic beta cells via intracellular and extracellular regulatory circuits.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in the degradation of the low-density lipoprotein receptor. PCSK9 also targets proteins involved in lipid metabolism (very low-density lipoprotein receptor), immunity (major histocompatibility complex I), and viral infection (cluster of differentiation 81). Recent studies have also indicated that PCSK9 loss-of-function mutations are associated with an increased incidence of diabetes; however, the expression and function of PCSK9 in insulin-producing pancreatic beta cells remain unclear. Here, we studied PCSK9 regulation and function by performing loss- and gain-of-function experiments in the human beta cell line EndoC-ßH1. We demonstrate that PCSK9 is expressed and secreted by EndoC-ßH1 cells. We also found that PCSK9 expression is regulated by cholesterol and sterol regulatory element-binding protein transcription factors, as previously demonstrated in other cell types such as hepatocytes. Importantly, we show that PCSK9 knockdown using siRNA results in deregulation of various elements of the transcriptome, proteome, and secretome, and increases insulin secretion. We also observed that PCSK9 decreases low-density lipoprotein receptor and very low-density lipoprotein receptor levels via an extracellular signaling mechanism involving exogenous PCSK9, as well as levels of cluster of differentiation 36, a fatty acid transporter, through an intracellular signaling mechanism. Finally, we found that PCSK9 regulates the cell surface expression of PDL1 and HLA-ABC, proteins involved in cell-lymphocyte interaction, also via an intracellular mechanism. Collectively, these results highlight PCSK9 as a regulator of multiple cell surface receptors in pancreatic beta cells.

Characterization of the Secretome, Transcriptome, and Proteome of Human ß Cell Line EndoC-ßH1.

Early diabetes research is hampered by limited availability, variable quality, and instability of human pancreatic islets in culture. Little is known about the human ß cell secretome, and recent studies question translatability of rodent ß cell secretory profiles. Here, we verify representativeness of EndoC-ßH1, one of the most widely used human ß cell lines, as a translational human ß cell model based on omics and characterize the EndoC-ßH1 secretome. We profiled EndoC-ßH1 cells using RNA-seq, data-independent acquisition, and tandem mass tag proteomics of cell lysate. Omics profiles of EndoC-ßH1 cells were compared to human ß cells and insulinomas. Secretome composition was assessed by data-independent acquisition proteomics. Agreement between EndoC-ßH1 cells and primary adult human ß cells was ∼90% for global omics profiles as well as for ß cell markers, transcription factors, and enzymes. Discrepancies in expression were due to elevated proliferation rate of EndoC-ßH1 cells compared to adult ß cells. Consistently, similarity was slightly higher with benign nonmetastatic insulinomas. EndoC-ßH1 secreted 783 proteins in untreated baseline state and 3135 proteins when stressed with nontargeting control siRNA, including known ß cell hormones INS, IAPP, and IGF2. Further, EndoC-ßH1 secreted proteins known to generate bioactive peptides such as granins and enzymes required for production of bioactive peptides. EndoC-ßH1 secretome contained an unexpectedly high proportion of predicted extracellular vesicle proteins. We believe that secretion of extracellular vesicles and bioactive peptides warrant further investigation with specialized proteomics workflows in future studies.

Facilitatory Effect of Intermittent Repetitive Transcranial Magnetic Stimulation on Perceptual Distortion of the Face.

Orofacial pain patients often report that the painful facial area is "swollen" without clinical signs - known as perceptual distortion (PD). The neuromodulatory effect of facilitatory repetitive transcranial magnetic stimulation (rTMS) on PD in healthy individuals was investigated, to provide further support that the primary somatosensory cortex (SI) is involved in facial PD. Participants were allocated to active (n = 26) or sham (n = 26) rTMS group in this case-control study. PD was induced experimentally by injecting local anesthesia (LA) in the right infraorbital region. PD was measured at baseline, 6 min after LA, immediately, 20 and 40 min after rTMS. Intermittent theta-burst stimulation (iTBS) as active rTMS and sham rTMS was applied to the face representation area of SI at 10 min after LA. The magnitude of PD was compared between the groups. The magnitude of PD significantly increased immediately after iTBS compared with sham rTMS (P = .009). The PD was significantly higher immediately after iTBS compared to 6 min after LA (P = .004) in the active rTMS group, but not in the sham rTMS group (P = .054). iTBS applied to a somatotopic-relevant cortical region appears to facilitate facial PD further supporting the involvement of SI in the processing of one´s own face and PD. PERSPECTIVE: This study provides information on neural substrate responsible for processing of perceptual distortion of the face which is speculated to contribute to the chronification of orofacial pain. The findings of this study may aid in mechanism-based management of the condition in orofacial pain disorders and possibly other chronic pain states.

A deep hybrid learning pipeline for accurate diagnosis of ovarian cancer based on nuclear morphology.

Nuclear morphological features are potent determining factors for clinical diagnostic approaches adopted by pathologists to analyze the malignant potential of cancer cells. Considering the structural alteration of the nucleus in cancer cells, various groups have developed machine learning techniques based on variation in nuclear morphometric information like nuclear shape, size, nucleus-cytoplasm ratio and various non-parametric methods like deep learning have also been tested for analyzing immunohistochemistry images of tissue samples for diagnosing various cancers. We aim to correlate the morphometric features of the nucleus along with the distribution of nuclear lamin proteins with classical machine learning to differentiate between normal and ovarian cancer tissues. It has already been elucidated that in ovarian cancer, the extent of alteration in nuclear shape and morphology can modulate genetic changes and thus can be utilized to predict the outcome of low to a high form of serous carcinoma. In this work, we have performed exhaustive imaging of ovarian cancer versus normal tissue and developed a dual pipeline architecture that combines the matrices of morphometric parameters with deep learning techniques of auto feature extraction from pre-processed images. This novel Deep Hybrid Learning model, though derived from classical machine learning algorithms and standard CNN, showed a training and validation AUC score of 0.99 whereas the test AUC score turned out to be 1.00. The improved feature engineering enabled us to differentiate between cancerous and non-cancerous samples successfully from this pilot study.

SAM 40: Dataset of 40 subject EEG recordings to monitor the induced-stress while performing Stroop color-word test, arithmetic task, and mirror image recognition task.

This paper presents a collection of electroencephalogram (EEG) data recorded from 40 subjects (female: 14, male: 26, mean age: 21.5 years). The dataset was recorded from the subjects while performing various tasks such as Stroop color-word test, solving arithmetic questions, identification of symmetric mirror images, and a state of relaxation. The experiment was primarily conducted to monitor the short-term stress elicited in an individual while performing the aforementioned cognitive tasks. The individual tasks were carried out for 25 s and were repeated to record three trials. The EEG was recorded using a 32-channel Emotiv Epoc Flex gel kit. The EEG data were then segmented into non-overlapping epochs of 25 s depending on the various tasks performed by the subjects. The EEG data were further processed to remove the baseline drifts by subtracting the average trend obtained using the Savitzky-Golay filter. Furthermore, the artifacts were also removed from the EEG data by applying wavelet thresholding. The dataset proposed in this paper can aid and support the research activities in the field of brain-computer interface and can also be used in the identification of patterns in the EEG data elicited due to stress.

CMOS-Based Electrokinetic Microfluidics With Multi-Modal Cellular and Bio-Molecular Sensing for End-to-End Point-of-Care System.

The importance of point-of-care (POC) bio-molecular diagnostics capable of rapid analysis has become abundantly evident after the outbreak of the Covid-19 pandemic. While sensing interfaces for both protein and nucleic-acid based assays have been demonstrated with chip-scale systems, sample preparation in compact form factor has often been a major bottleneck in enabling end-to-end POC diagnostics. Miniaturization of an end-to-end system requires addressing the front-end sample processing, without which, the goal for low-cost POC diagnostics remain elusive. In this paper, we address bulk fluid processing with AC-osmotic based electrokinetic fluid flows that can be fully controlled, processed and automated by CMOS ICs, fabricated in TSMC 65 nm LP process. Here, we combine bulk fluid flow control with bio-molecular sensing, cell manipulation, cytometry, and separation-all of which are controlled with silicon chips for an all-in-one bio-sensing device. We show CMOS controlled pneumatic-free bulk fluid flow with fluid velocities reaching up to 160 µm/s within a microfluidic channel of 100 × 50 µm 2 of cross-sectional area. We incorporate electrode arrays to allow precise control and focused cell flows ( ±2 µm precision) for robust cytometry, and for subsequent separation. We also incorporate a 16-element impedance spectroscopy receiver array for cell and label-free protein sensing. The massive scalability of CMOS-driven microfluidics, manipulation, and sensing can lead to a new design space and a new class of miniaturized sensing technologies.

Desloratadine Exposure and Incidence of Seizure: A Nordic Post-authorization Safety Study Using a New-User Cohort Study Design, 2001-2015.

INTRODUCTION: A small number of adverse events of seizure in patients using desloratadine (DL) have been reported. The European Medicines Agency requested a post-authorization safety study to investigate whether there is an association between DL exposure and seizure. OBJECTIVE: The aim was to study the association between DL exposure and incidence of first seizure. METHODS: A new-user cohort study of individuals redeeming a first-ever prescription of DL in Denmark, Finland, Norway, and Sweden in 2001-2015 was conducted. DL exposure was defined as days' supply plus a 4-week grace period. DL unexposed periods were initiated 27 weeks after DL prescription redemption. Poisson regression was used to estimate the adjusted incidence rate and adjusted incidence rate ratio (aIRR) of incident seizure. RESULTS: A total of 1,807,347 first-ever DL users were included in the study, with 49.3% male and a mean age of 29.5 years at inclusion; 20.3% were children aged 0-5 years. The adjusted incidence rates of seizure were 21.7 and 31.6 per 100,000 person-years during DL unexposed and exposed periods, respectively. A 46% increased incidence rate of seizure was found during DL exposed periods (aIRR = 1.46, 95% confidence interval [CI] 1.34-1.59). The aIRR ranged from 1.85 (95% CI 1.65-2.08) in children aged 0-5 years to 1.01 in adults aged 20 years or more (95% CI 0.85-1.19). CONCLUSION: This study found an increased incidence rate of seizure during DL exposed periods as compared to unexposed periods among individuals younger than 20 years. No difference in incidence rate of seizure was observed in adults between DL exposed and unexposed.

Pulling the springs of a cell by single-molecule force spectroscopy.

The fundamental unit of the human body comprises of the cells which remain embedded in a fibrillar network of extracellular matrix proteins which in turn provides necessary anchorage the cells. Tissue repair, regeneration and reprogramming predominantly involve a traction force mediated signalling originating in the ECM and travelling deep into the cell including the nucleus via circuitry of spring-like filamentous proteins like microfilaments or actin, intermediate filaments and microtubules to elicit a response in the form of mechanical movement as well as biochemical changes. The 'springiness' of these proteins is highlighted in their extension-contraction behaviour which is manifested as an effect of differential traction force. Atomic force microscope (AFM) provides the magic eye to visualize and quantify such force-extension/indentation events in these filamentous proteins as well as in whole cells. In this review, we have presented a summary of the current understanding and advancement of such measurements by AFM based single-molecule force spectroscopy in the context of cytoskeletal and nucleoskeletal proteins which act in tandem to facilitate mechanotransduction.

Emerging roles of lamins and DNA damage repair mechanisms in ovarian cancer.

Lamins are type V intermediate filament proteins which are ubiquitously present in all metazoan cells providing a platform for binding of chromatin and related proteins, thereby serving a wide range of nuclear functions including DNA damage repair. Altered expression of lamins in different subtypes of cancer is evident from researches worldwide. But whether cancer is a consequence of this change or this change is a consequence of cancer is a matter of future investigation. However changes in the expression levels of lamins is reported to have direct or indirect association with cancer progression or have regulatory roles in common neoplastic symptoms like higher nuclear deformability, increased genomic instability and reduced susceptibility to DNA damaging agents. It has already been proved that loss of A type lamin positively regulates cathepsin L, eventually leading to degradation of several DNA damage repair proteins, hence impairing DNA damage repair pathways and increasing genomic instability. It is established in ovarian cancer, that the extent of alteration in nuclear morphology can determine the degree of genetic changes and thus can be utilized to detect low to high form of serous carcinoma. In this review, we have focused on ovarian cancer which is largely caused by genomic alterations in the DNA damage response pathways utilizing proteins like RAD51, BRCA1, 53BP1 which are regulated by lamins. We have elucidated the current understanding of lamin expression in ovarian cancer and its implications in the regulation of DNA damage response pathways that ultimately result in telomere deformation and genomic instability.