Biology subjects

Islam, R.

Publications and source records attributed to Islam, R..

At least 19 recordsLinked to original sources

bioRxiv2026

XPO1 Inhibition by Selinexor Induces Nuclear p53 and p21 Accumulation, Cell-Cycle Arrest and Apoptosis in Testicular Germ Cell Tumors

Background: Testicular germ cell tumors (TGCTs) are the most common solid malignancies in young men. Despite high cure rates with cisplatin-based chemotherapy, resistance and long-term toxicities remain clinical challenges in TGCTs. Selinexor, an FDA-approved XPO1 inhibitor, has demonstrated anti-tumor activity in other cancers, but its potential in TGCTs remains unknown. Objective: We investigated the antitumor effects of selinexor in TGCT cell lines. Materials and methods: XPO1 RNA expression, protein abundance and localization were evaluated by immunohistochemistry in TGCT tissue microarrays and non-neoplastic testicular tissues, and by meta-analysis of publicly available gene-expression microarray datasets from normal testis, primary TGCT specimens as well as TGCT cell lines. Selinexor effects on cell viability, cell-cycle distribution and apoptosis were evaluated using XTT assay and flow cytometry. p53 and p21 expression and localization were analyzed by Western blotting and Immunofluorescence. Results: XPO1 expression was heterogeneous across normal testis, TGCT tissues and cell lines. Yet, selinexor reduced TGCT cell viability and induced G1 or G2/M cell-cycle arrest, apoptosis, increased total p53 and p21 protein levels, and their nuclear accumulation. Of note, control fibroblast exhibited limited sensitivity to selinexor. Discussion and conclusion: Our findings demonstrate that inhibition of XPO1 with selinexor might be potential therapeutic strategy for TGCTs.

cancer biology↗

bioRxiv2026

G-quadruplex targeting by CX-5461 as a novel therapeutic strategy in testicular germ cell tumors

Testicular germ cell tumors (TGCTs) are highly curable malignancies; however, resistance to cisplatin-based therapy remains a critical clinical challenge. G-quadruplexes (G4s) are specific guanine rich, four-stranded DNA structures that are enriched at distinct genomic regions. Due to their stability, G4s can influence genome stability, gene expression, DNA replication as well as telomere maintenance. G4 stabilization by small molecules has been shown to have anticancer effects in several tumors but remains underexplored in TGCTs. Here, we systematically evaluated the effect of six different G4- ligands (CX-5461, CX-3543, BRACO19, PDS, CM03 and RHPS4) on TGCT cell lines and non-malignant fibroblasts. Among those G4 ligands, CX-5461 showed strongest cellular changes in TGCTs. We observed dose- and time-dependent G4 stabilization upon CX-5461 treatment in TGCT cells, accompanied by impaired RNA polymerase I-dependent transcription and induction of DNA double-strand breaks, whereas only minimal effects were observed in control fibroblasts. These effects led to the activation of p53 signaling, and consequently an upregulation of canonical p53 target genes, including CDKN1A, MDM2, PIDD1, GADD45A, ZMAT3, SESN1 and PPM1D, resulting in G2/M cell-cycle arrest and apoptosis. The presence of potential quadruplex forming sequences (PQSs) in the promoters or gene bodies of these genes suggests that G4 structures may contribute to the p53 transcriptional response. Collectively, these data demonstrate that CX-5461 appears as highly potent G4-ligand inducing p53-dependent molecular cascades leading to cell death in germ cell tumors. Unlike in many other tumors, p53 remains functionally intact in TGCTs, suggesting that CX-5461-mediated activation of the p53 pathway could be selectively targeted as a therapeutic strategy in TGCTs.

cancer biology↗

bioRxiv2025

ProtSEC: Ultrafast Protein Sequence Embedding in Complex Space Using Fast Fourier Transform

Among the various approaches for representing protein sequences as vectors, embeddings derived from protein language models (PLMs) have been empirically shown to enhance accuracy in downstream bioinformatics tasks. However, the substantial computational demands of PLMs, both during training and inference, pose significant challenges. We introduce ProtSEC (Protein Sequence Embedding in Complex Space), a novel approach that encodes each amino acid as a unique complex number derived from the BLOSUM62 substitution matrix. By modeling protein sequences as complex signals and applying the Fast Fourier Transform (FFT), ProtSEC generates embeddings in the complex space. Unlike PLMs, ProtSEC requires no pre-training on large protein sequence datasets and operates independently of any pre-trained models. Our benchmarking demonstrate that ProtSEC achieves a 20,000-fold reduction in runtime and an 85-fold improvement in memory efficiency compared to popular PLMs (e.g., esm2_3B, esm2_35M, prot_t5, prot_bert). Depending on the task, ProtSEC demonstrates either superior or comparable accuracy to PLMs in sequence similarity search, sequence classification and phylogenetic tree reconstruction. ProtSEC provides fast and accurate protein sequence embeddings in complex numbers, facilitating efficient integration into diverse downstream bioinformatics workflows. ProtSEC is available at https://github.com/omics-lab/ProtSEC.

bioinformatics↗

bioRxiv2024

Postnatal Enrichment Corrects Deficits in Perineuronal Net Formation and Reversal Learning in Adult Mice Exposed to Early Adversity

Withdrawal StatementThe authors have withdrawn this manuscript because the behavioral studies using the Barnes maze were not conducted according to the methods described, specifically regarding the animals ability to locate the escape hole independently. Furthermore, the authors were unable to replicate the behavioral outcomes originally reported when the experiments were repeated following the stated methods. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

neuroscience↗

bioRxiv2024

Transient Impairment in Microglial Function Causes Sex-Specific Deficits in Synaptic and Hippocampal Function in Mice Exposed to Early Adversity

Abnormal development and function of the hippocampus are two of the most consistent findings in humans and rodents exposed to early life adversity, with males often being more affected than females. Using the limited bedding (LB) paradigm as a rodent model of early life adversity, we found that male adolescent mice that had been exposed to LB exhibit significant deficits in contextual fear conditioning and synaptic connectivity in the hippocampus, which are not observed in females. This is linked to altered developmental refinement of connectivity, with LB severely impairing microglial-mediated synaptic pruning in the hippocampus of male and female pups on postnatal day 17 (P17), but not in adolescent P33 mice when levels of synaptic engulfment by microglia are substantially lower. Since the hippocampus undergoes intense synaptic pruning during the second and third weeks of life, we investigated whether microglia are required for the synaptic and behavioral aberrations observed in adolescent LB mice. Indeed, transient ablation of microglia from P13-21, in normally developing mice caused sex-specific behavioral and synaptic abnormalities similar to those observed in adolescent LB mice. Furthermore, chemogenetic activation of microglia during the same period reversed the microglial-mediated phagocytic deficits at P17 and restored normal contextual fear conditioning and synaptic connectivity in adolescent LB male mice. Our data support an additional contribution of astrocytes in the sex-specific effects of LB, with increased expression of the membrane receptor MEGF10 and enhanced synaptic engulfment in hippocampal astrocytes of 17-day-old LB females, but not in LB male littermates. This finding suggests a potential compensatory mechanism that may explain the relative resilience of LB females. Collectively, these studies highlight a novel role for glial cells in mediating sex-specific hippocampal deficits in a mouse model of early-life adversity.

neuroscience↗

bioRxiv2023

Characterization of β-lactamase and virulence genes in Pseudomonas aeruginosa isolated from clinical, environmental and poultry sources in Bangladesh

The emergence and spread of multidrug-resistant pathogens like Pseudomonas aeruginosa are major concerns for public health worldwide. This study aimed to investigate the prevalence of circulating P. aeruginosa isolated from clinical, environmental and poultry sources in Bangladesh, their antibiotic susceptibility, {beta}-lactamase and virulence gene profiling using standard molecular and microbiology techniques. We collected 110 samples from five different locations, viz., BAU residential area (BAURA; n=15), BAU Healthcare Center (BAUHCC; n = 20), BAU Veterinary Teaching Hospital (BAUVTH; n=22), Poultry Market (PM; n=30) and Mymensingh Medical College Hospital (MCCH; n=23). After overnight enrichment in nutrient broth, 89 probable Pseudomonas isolates (80.90%) were screened through selective culture, gram-staining and biochemical tests. Using genus- and species-specific PCR, we confirmed 22 isolates (20.0%) as P. aeruginosa from these samples. Antibiogram profiling revealed that 100.0% P. aeruginosa isolates (n = 22) were multidrug-resistant isolates, showing resistance against Doripenem, Penicillin, Ceftazidime, Cefepime, and Imipenem. Furthermore, resistance to aztreonam was observed in 95.45% isolates. However, P. aeruginosa isolates showed a varying degree of sensitivity against Amikacin, Gentamicin, and Ciprofloxacin. The blaTEM gene was detected in 86.0% isolates, while blaCMY, blaSHV and blaOXA, were detected in 27.0%, 18.0% and 5.0% of the P. aeruginosa isolates, respectively. The algD gene was detected in 32.0% isolates, whereas lasB and exoA genes were identified in 9.0% and 5.0% P. aeruginosa isolates. However, none of the P. aeruginosa isolates harbored exoS gene. Thus, this study provides novel and important data on the resistance and virulence of P. aeruginosa currently circulating in clinical, environmental and poultry environment of Bangladesh. These data provide important insights into the emergence of {beta}-lactamase resistance in P. aeruginosa, highlighting its usefulness in the treatment and control of P. aeruginosa infections in both humans and animals.

microbiology↗

bioRxiv2023

T cells in testicular germ cell tumors: new evidence of fundamental contributions by rare subsets

BACKGROUNDImmune cell infiltration is heterogeneous but common in testicular germ cell tumors (TGCT) and pre-invasive germ cell neoplasia in situ (GCNIS). Tumor-infiltrating T cells including regulatory T (Treg) and follicular helper T (Tfh) cells are found in other cancer entities, but their contributions to TGCT are unknown. METHODSHuman testis specimens from independent patient cohorts were analyzed using immunohistochemistry, flow cytometry and single-cell RNA sequencing (scRNA-seq) with special emphasis on delineating T cell subtypes. RESULTSProfound changes in immune cell composition within TGCT, shifting from macrophages in normal testes to T cells plus B and dendritic cells in TGCT, were documented. In most samples (96%), the CD4+ T cell frequency exceeded that of CD8+ cells, with decreasing numbers from central to peripheral tumor areas, and to tumor-free, contralateral testes. T cells including Treg and Tfh were most abundant in seminoma compared to mixed tumors and embryonal carcinoma. CONCLUSIONDespite considerable heterogeneity between patients, T cell subtypes form a key part of the TGCT microenvironment. The novel finding of rare Treg and Tfh cells in human testis suggests their involvement in TGCT pathobiology, with implications for understanding tumor progression, to assess patients prognosis, and as putative targets for personalized immunotherapy.

cancer biology↗

bioRxiv2023

Early Deprivation Impairs Perforant Pathway Connectivity and Contextual Memory in Adolescent Male Mice

Early-life adversity causes reduced hippocampal volume and abnormal hippocampal connectivity and function, with evidence indicating more prominent deficits in males compared to females. Reelin-positive projections from the lateral entorhinal cortex (LEC) to the dorsal hippocampus are essential for encoding contextual and semantic memories in diverse mammalian species, including humans and rodents. However, the impact of early-life adversity on these projections and their contribution to hippocampal-dependent deficits have not been reported. Using a modified limited bedding (LB) mouse model of early adversity that extends the impoverished conditions from birth to postnatal day 25 (P25), we found severe impairment in contextual fear conditioning for adolescent LB male but not LB female mice. Using retrograde tracing, we found that the number of reeling-positive projections from the LEC to the dorsal hippocampus is significantly reduced in LB males but not LB females. Further, the number of projections was highly correlated with deficits in contextual memory and hypomyelination in perforant pathway terminals located in the dorsal hippocampus. Ex vivo high-resolution diffusion magnetic resonance imaging confirmed reduced structural connectivity between the entorhinal cortex and the dorsal hippocampus and revealed extensive cortical atrophy that resembled abnormalities reported in children exposed to severe deprivation. Given the essential role that reelin-positive projections play in contextual memory, these findings suggest a novel mechanism to explain the pronounced contextual memory deficits seen in LB males.

neuroscience↗

bioRxiv2023

Identification of Therapeutic Leads from Ficus hispida Fruit Phytochemicals against Prostate Cancer Using Pharmacoinformatic and Molecular Dynamics Simulation Approach

Prostate cancer is one of the leading causes of death and the most common cancer type in men. In this study, potential leads from the phytochemicals of Ficus hispida fruit were screened using in silico tools against androgen receptor (AR), a known target for prostate cancer. PASS online and ADMET tools were used to screen specific phytochemicals that are relevant to prostate cancer treatment and have drug-like properties. Of 13, a total of 10 phytochemicals passed PASS online and ADMET screening. Next, a total of three phytochemicals, including nodakenetin (CID: 26305), isowigtheone hydrate (CID: 66728267), and 7-hydroxycoumarin (CID: 5281426) were selected based on their docking scores (-9.946 to -7.653 kcal/mol) and relevance to selective bioactivity. The MD simulation further confirmed the binding stability of these three phytochemicals with their target AR protein and determined that the main amino acid residues mainly responsible for this stability including RMSD, RMSF, and post simulation binding free energies. These findings suggest that these three phytochemicals of Ficus hispida fruit can further be developed as prospective therapeutics against prostate cancer.

bioinformatics↗

bioRxiv2023

Computational investigation of Scutellarein derivatives as an inhibitor against triple-negative breast cancer by Quantum calculation, and drug-designed approaches

Triple-negative breast cancer accounts for 10-15% of all breast tumors (TNBC). Triple-negative breast cancer lacks either estrogen or progesterone receptors (ER or PR), producing either too little or too much HER2. (All three tests result in "negative" results for the cells.) These cancers are more common in women under 40 who are Black or have the BRCA1 mutation. TNBC differs from other types of invasive breast cancer in that it has fewer treatment options, a worse prognosis, and grows and spreads more quickly (outcome). So, first of all, the protein of triple-negative breast cancer was collected from the PDB database having the most stable configuration, and a natural bioactive molecule, Scutellarein, was selected. Scutellarein is well-known to possess anti-cancer properties, so its derivatives were chosen to design anticancer drugs through computational tools. In this case, the functional group has applied and modified structural activity relationship methods. Then, the pass prediction score was taken, which indicates the probability of active (Pa) and the probability of inactive (Pi). After that, other in-silco approaches, such as the ADMET parameter, and quantum calculation by Density Functional Theory (DFT), have been conducted. Finally, molecular docking and dynamics have been evaluated against TNBC to determine the binding affinity and stability. Scutellarein derivatives (DM03 at -10.7 kcal/mol, DM04 at -11.0 kcal/mol) have been reported to have a maximum tendency for binding against TNBC. Besides, the molecular dynamic simulation was performed at 100ns and described by root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF), which are much more stable compounds. The pharmacokinetics specifications for a suitable therapeutic candidate were satisfied by these molecules, like as non-carcinogenic, minimal to aquatic and non-aquatic toxicity. Almost all the molecules are highly soluble in the aqueous system. These all-computational data suggested that they might be suitable as a medication for the inhibition of TNBC, and further experimental studies should be carried out.

bioinformatics↗

bioRxiv2023

Mass spectrometric analysis and biostimulatory effects of boar seminal gel, saliva and semen in pigs

The present study aimed to identify novel biostimulatory compounds in boar seminal gel (SG), saliva and semen using Gas chromatography-mass spectrometry (GC-MS). SG alone and its combined application with saliva (SG+saliva) and semen (SG+semen) also studied to train young boars. SG alone and SG+Saliva investigated for estrus induction in gilts and sows. Distilled water (DW) exposure was kept as control. SG, saliva and semen screened for total 105, 96 and 89 compounds. The highest concentration was of alkanes followed by sugar alcohols, then hydrocarbons, amino acids and fatty acids. Elaidic acid is the novel compound identified in pigs. Other compounds were tridecenol, undecane, hexadecone, eicosane, tetracosane etc. Further, young males (64.86%) were able to get trained. Significant higher (p<0.05) number of males got trained in exposure to SG (80%), SG+saliva (75%) and SG+semen (75%) than control. The time (hrs) taken by young boars to get trained on exposure to combination of SG+saliva (244{+/-}22.19) and SG+semen (216{+/-}13.14) was lesser (p<0.05) than SG (356{+/-}61.85) alone. Interval (hrs) for exhibition of different sexual behaviour by males on exposure to SG, saliva and semen was lesser (p<0.05) than control. Estrus was induced in 61.25% of females. Significant (p<0.05) higher number of females showed estrus response to exposure of SG (72.72%) and SG+saliva (69.23%) than control. Interval taken to exhibit estrus was lesser (p<0.05) in females exposed to SG+saliva (201.88{+/-}12.66) than SG (262.14{+/-}20.06) alone. Interval (hrs) for exhibition of different sexual behaviour by females on exposure to SG+saliva was lesser (p<0.05) than control. In conclusion, novel compounds with biostimulatory properties have been identified in boar SG, saliva and semen. The combined exposure of SG with saliva and semen have more intense biostimulation effect than SG alone. Such compounds and biostimulatory effects can be exploited for augmenting reproductive efficiency in pigs.

animal behavior and cognition↗

bioRxiv2023

Hormonal Interventions for optimizing reproductive efficiency in pigs at Farmers field

ObjectiveOptimizing reproductive efficiency in terms of estrus induction and production performance using simplified hormonal intervention using GnRH, gonadotropins and progesterone at farmers field conditions to bred animals with superior quality semen and also to reduce the maintenance cost. MethodThe present study was planned for optimizing reproductive efficiency using four different easily available hormonal agents with simplified protocols at farmers field. A total of 126 females were used in the study. Hormonal protocols I, II, III and IV using GnRH + (PMSG+ hCG), (PMSG+ hCG), PMSG alone and prepared progesterone gel respectively were used for estrus induction in gilts and sows. ResultsThe estrus induction/rate was (77.77%, 81.36%, 78.57% and 50% respectively. The corresponding figures for interval (hrs) of heat exhibition from hormonal administration (121.33{+/-}4.93, 121.54{+/-}3.60, 78.52{+/-}4.52 and 192{+/-}24), conception rate (%) (72.22%, 81.25%, 68.18% and 33.33%) farrowing rate (55.55%, 68.29%, 68.18% and 33.33 %), total litter size at birth (7.2{+/-}0.64, 7.90{+/-}0.47, 8.90{+/-}0.47 and 7.00{+/-}0) and hormonal cost (Rs.) per animal (570, 335, 280 and 250 Rs.) were respectively. The easier to use protocol was III followed by II, I and IV. ConclusionIt was found that protocol II and III are effective and easier so can be used for optimizing reproductive efficiency in pigs at farmers field.

physiology↗

bioRxiv2021

VirusTaxo: Taxonomic classification of virus genome using multi-class hierarchical classification by k-mer enrichment

Taxonomic classification of viruses is a multi-class hierarchical classification problem, as taxonomic ranks (e.g., order, family and genus) of viruses are hierarchically structured and have multiple classes in each rank. Classification of biological sequences which are hierarchically structured with multiple classes is challenging. Here we developed a machine learning architecture, VirusTaxo, using a multi-class hierarchical classification by k-mer enrichment. VirusTaxo classifies DNA and RNA viruses to their taxonomic ranks using genome sequence. To assign taxonomic ranks, VirusTaxo extracts k-mers from genome sequence and creates bag-of-k-mers for each class in a rank. VirusTaxo uses a top-down hierarchical classification approach and accurately assigns the order, family and genus of a virus from the genome sequence. The average accuracies of VirusTaxo for DNA viruses are 99% (order), 98% (family) and 95% (genus) and for RNA viruses 97% (order), 96% (family) and 82% (genus). VirusTaxo can be used to detect taxonomy of novel viruses using full length genome or contig sequences. AvailabilityOnline version of VirusTaxo is available at https://omics-lab.com/virustaxo/.

bioinformatics↗

bioRxiv2021

HolistiC: Leveraging Hi-C and Whole Genome Shotgun Sequencing for Double Minute Chromosome Discovery

Double minute chromosomes are acentric extrachromosomal DNA artifacts that are frequently observed in the cells of numerous cancers. They are highly amplified and contain oncogenes and drug resistance genes, making their presence a challenge for effective cancer treatment. Algorithmic discovery of double minutes (DM) can potentially improve bench-derived therapies for cancer treatment. A hindrance to this task is that DMs evolve, yielding circular chromatin that shares segments from progenitor double minutes. This creates double minutes with overlapping amplicon coordinates. Existing DM discovery algorithms use whole genome shotgun sequencing in isolation, which can potentially incorrectly classify DMs that share overlapping coordinates. In this study, we describe an algorithm called " HolistIC" that can predict double minutes in tumor genomes by integrating whole genome shotgun sequencing (WGS) and Hi-C sequencing data. The consolidation of these sources of information resolves ambiguity in double minute amplicon prediction that exists in DM prediction with WGS data used in isolation. We implemented and tested our algorithm on the tandem Hi-C and WGS datasets of three cancer datasets and a simulated dataset. Results on the cancer datasets demonstrated HolistICs ability to predict DMs from Hi-C and WGS data in tandem. The results on the simulated data showed the HolistIC can accurately distinguish double minutes that have overlapping amplicon coordinates, an advance over methods that predict extrachromosomal amplification using WGS data in isolation. AvailabilityOur software is available at http://www.github.com/mhayes20/HolistIC.

bioinformatics↗

bioRxiv2020

Choice of assemblers has a critical impact on de novo assembly of SARS-CoV-2 genome and characterizing variants

BackgroundCoronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic following its initial emergence in China. Using next-generation sequencing technologies, a large number of SARS-CoV-2 genomes are being sequenced at an unprecedented rate and being deposited in public repositories. For the de novo assembly of the SARS-CoV-2 genomes, a myriad of assemblers is being used, although their impact on the assembly quality has not been characterized for this virus. In this study, we aim to understand the variabilities on assembly qualities due to the choice of the assemblers. ResultsWe performed 6,648 de novo assemblies of 416 SARS-CoV-2 samples using 8 different assemblers with different k-mers. We used Illumina paired-end sequencing reads and compared the genome assembly quality to that of different assemblers. We showed the choice of assemblers plays a significant role in reconstructing the SARS-CoV-2 genome. Two metagenomic assemblers e.g. MEGAHIT and metaSPAdes performed better compared to others in most of the assembly quality metrics including, recovery of a larger fraction of the genome, constructing larger contigs and higher N50, NA50 values etc. We showed that at least 09% (259/2,873) of the variants present in the assemblies between MEGAHIT and metaSPAdes are unique to the assembly methods. ConclusionOur analyses indicate the critical role of assembly methods for assembling SARS-CoV-2 genome using short reads and their impact on variant characterization. This study could help guide future studies to determine which assembler is best suited for the de novo assembly of virus genomes.

bioinformatics↗

bioRxiv2020

The Coding And Small-Non-Coding Hippocampal Synaptic RNAome

Neurons are highly compartmentalized cells that depend on local protein synthesis. Thus, messenger RNAs (mRNAs) have been detected in neuronal dendrites and more recently also at the pre- and postsynaptic compartment. Other RNA species, such as microRNAs, have also been described at synapses where they are believed to control mRNA availability for local translation. Nevertheless, a combined dataset analyzing the synaptic coding and non-coding RNAome via next-generation sequencing approaches is missing. Here we isolate synaptosomes from the hippocampus of young wild type mice and provide the coding and non-coding synaptic RNAome. These data are complemented by a novel approach to analyze the synaptic RNAome from primary hippocampal neurons grown in microfluidic chambers. Our data show that synaptic microRNAs control almost the entire synaptic mRNAome and we identified several hub microRNAs. By combining the in vivo synaptosomal data with our novel microfluidic chamber system, we also provide evidence to support the hypothesis that part of the synaptic microRNAome may be supplied to neurons via astrocytes. Moreover, the microfluidic system is suitable to study the dynamics of the synaptic RNAome in response to stimulation. In conclusion, our data provide a valuable resource and hint to several important targets for future experiments.

neuroscience↗

bioRxiv2020

Spectrin Interactome under normal and HbE-disease conditions

Spectrin, the major component of the erythrocyte membrane skeleton is a key player in red cell biology. It has a significant role in signalling pathways and as such knowledge of spectrin interactors becomes crucial. Here we report the cytosolic interactome of human erythroid spectrin (ProteomeXchange id: PXD021525). This is to the best of our knowledge the first report of the interactome of human erythroid spectrin. We have further investigated the spectrin interactome under HbE disease conditions. Our findings indicate that there is no difference in the identity of the proteins interacting with spectrin between normal and disease conditions. However relative abundance of the interacting partners is seen to change. Very interestingly the interacting chaperone proteins, heme-containing proteins and redox active proteins are seen to be up-regulated in HbE disease state. This is consistent with our previous observation that presence of oxidation prone hemoglobin variants leads to an increase of redox regulators and chaperones in the red cell proteome. Spectrin can also interact with horse radish peroxidase and oxidatively crosslink hemoglobin, which has possible implications in oxidative stress management. Since a large fraction of spectrin interacting proteins are chaperones and redox active proteins, it is possible that spectrin may have a broader role in redox regulation, especially in cases where there are unstable hemoglobin variants present.

biochemistry↗

bioRxiv2020

Newly regenerated axons through a cell-containing biomaterial scaffold promote reorganization of spinal circuitry and restoration of motor functions with epidural electrical stimulation.

We report the effect of newly regenerated neural fibers via bioengineered scaffold on reorganization of spinal circuitry and restoration of motor functions with electrical epidural stimulation (EES) after spinal transection (ST). Restoration across multiple modalities was evaluated for 7 weeks after ST with implanted scaffold seeded with Schwann cells, producing neurotrophic factors and with rapamycin microspheres. Gradual improvement in EES-facilitated stepping was observed in animals with scaffolds, although, no significant difference in stepping ability was found between groups without EES. Similar number of regenerated axons through the scaffolds was found in rats with and without EES-enabled training. Re-transection through the scaffold at week 6, reduced EES-enabled motor function, remaining higher compared to rats without scaffolds. The combination of scaffolds and EES-enabled training demonstrated synaptic changes below the injury. These findings indicate that sub-functional connectivity with regenerated across injury fibers can reorganize of sub-lesional circuitry, facilitating motor functions recovery with EES.

neuroscience↗