Biology subjects

Khan, A.

Publications and source records attributed to Khan, A..

At least 181 records · Page 10Linked to original sources

bioRxiv2020

A simple method for isolating high-quality RNA from kenaf containing high polysaccharide and polyphenol contents

The isolation of high-quality RNA from kenaf is crucial for genetic and molecular biology studies. However, high levels of polysaccharide and polyphenol compounds in kenaf tissues could irreversibly bind to and coprecipitate with RNA, which complicates RNA extraction. In the present study, we proposed a simplified, time-saving and low-cost extraction method for isolating high quantities of high-quality RNA from several different kenaf tissues. RNA quality was measured for yield and purity, and the proposed protocol yielded high quantities of RNA (10.1-12.9 μg/g·FW). Spectrophotometric analysis showed that A260/280 ratios of RNA samples were in the range of 2.11 to 2.13, and A260/230 ratios were in the range of 2.04-2.24, indicating that the RNA samples were free of polyphenols, polysaccharides, and protein contaminants after isolation. The method of RNA extraction presented here was superior to the conventional CTAB method in terms of RNA isolation efficiency and was more sample-adaptable and cost-effective than commercial kits. Furthermore, to confirm downstream amenability, the high-quality RNA obtained from this method was successfully used for RT-PCR, real-time RT-PCR and Northern blot analysis. We provide an efficient and low-cost method for extracting high quantities of high-quality RNA from plants that are rich in polyphenols and polysaccharides, and this method was also validated for the isolation of high-quality RNA from other plants.View Full Text

genetics↗

bioRxiv2020

Inferring cellular trajectories from scRNA-seq using Pseudocell Tracer

Single cell RNA sequencing (scRNA-seq) can be used to infer a temporal ordering of dynamic cellular states. Current methods for the inference of cellular trajectories rely on unbiased dimensionality reduction techniques. However, such biologically agnostic ordering can prove difficult for modeling complex developmental or differentiation processes. The cellular heterogeneity of dynamic biological compartments can result in sparse sampling of key intermediate cell states. This scenario is especially pronounced in dynamic immune responses of innate and adaptive immune cells. To overcome these limitations, we develop a supervised machine learning framework, called Pseudocell Tracer, which infers trajectories in pseudospace rather than in pseudotime. The method uses a supervised encoder, trained with adjacent biological information, to project scRNA-seq data into a low-dimensional cellular state space. Then a generative adversarial network (GAN) is used to simulate pesudocells at regular intervals along a virtual cell-state axis. We demonstrate the utility of Pseudocell Tracer by modeling B cells undergoing immunoglobulin class switch recombination (CSR) during a prototypic antigen-induced antibody response. Our results reveal an ordering of key transcription factors regulating CSR, including the concomitant induction of Nfkb1 and Stat6 prior to the upregulation of Bach2 expression. Furthermore, the expression dynamics of genes encoding cytokine receptors point to the existence of a regulatory mechanism that reinforces IL-4 signaling to direct CSR to the IgG1 isotype.

bioinformatics↗

bioRxiv2020

Single-axon level automatic segmentation and feature extraction from immuhistochemical images of peripheral nerves

Quantitative descriptions of the morphology and structure of peripheral nerves is central in the development of bioelectronic devices interfacing the nerves. While histological procedures and microscopy techniques yield high-resolution detailed images of individual axons, automated methods to extract relevant information at the single-axon level are not widely available. We implemented a segmentation algorithm that allows for subsequent feature extraction in immunohistochemistry (IHC) images of peripheral nerves at the single fiber scale. These features include short and long cross-sectional diameters, area, perimeter, thickness of surrounding myelin and polar coordinates of single axons within a nerve or nerve fascicle. We evaluated the performance of our algorithm using manually annotated IHC images of 27 fascicles of the swine cervical vagus; the accuracy of single-axon detection was 82%, and of the classification of fiber myelination was 89%.

neuroscience↗

bioRxiv2020

Biodegradation of polyester polyurethane by Aspergillus flavus G10

Polyurethanes (PU) are integral to many aspects of our daily lives. Due to the extensive use of and difficulties in recycling or reusing PU, it mostly accumulates as waste. Various bacteria and fungi have been reported to degrade PU. We examined the fungus Aspergillus flavus G10 in that regard, after isolating it from the guts of Gryllus bimaculatus, a common cricket species. We observed surficial and chemical changes of PU with atomic force microscopy, scanning electron microscopy, and attenuated total reflectance Fourier-transform infrared spectroscopy. We measured physical changes as loss in tensile stress, stretching force, and weight of PU after incubations. Fungal hydrolysis of urethane bonds in the polymer backbone was demonstrated by detecting the formation of methylene di-aniline during incubations. Trapped CO2 during incubations equaled 52.6% of PU carbon. Biodegradation of PU was maximal by fungi cultured on a malt extract medium at 25 °C, pH 12, and 14:10 hrs light to dark ratio. Pretreating PU films with UV light or 1% FeSO4 or NaCl solutions further enhanced the rate of biodegradation. A range of techniques are needed to fully characterize the degradation of PU or other plastic polymers and to optimize conditions for their microbial degradation.View Full Text

bioengineering↗

bioRxiv2020

Convergence of cortical types and functional motifs in the mesiotemporal lobe

AO_SCPLOWBSTRACTC_SCPLOWThe parahippocampus-hippocampus complex in the mesiotemporal lobe (MTL) is implicated in many different cognitive processes, is compromised in numerous disorders, and exhibits a unique cytoarchitectural transition from six-layered isocortex to three-layered allocortex. Our study leveraged an ultra-high-resolution histological reconstruction of a human brain to (i) develop a continuous surface model of the MTL iso-to-allocortex transition and (ii) quantitatively characterise the regions cytoarchitecture. We projected the model into the native space of in vivo functional magnetic resonance imaging of healthy adults to (iii) construct a generative model of its intrinsic circuitry and (iv) determine its relationship with distributed functional dynamics of macroscale isocortical fluctuations. We provide evidence that the most prominent axis of cytoarchitectural differentiation of the MTL follows infolding from iso-to-allocortex and is defined by depth-specific variations in neuron density. Intrinsic effective connectivity exhibited a more complex relationship to MTL geometry, varying across both iso-to-allocortical and anterior-posterior axes. Variation along the long axis of the MTL was associated with differentiation between transmodal and unimodal systems, with anterior regions linked to transmodal cortex. In contrast, the iso-to-allocortical gradient was associated with the multiple demand system, with isocortex linked to regions activated when task demands prohibit the use of prior knowledge. Our findings establish a novel model of the MTL, in which its broad influence on neural function emerges through the combination micro- and macro-scale structural features. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/148643v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@48dbc7org.highwire.dtl.DTLVardef@15500a2org.highwire.dtl.DTLVardef@19c99b2org.highwire.dtl.DTLVardef@2eab49_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2020

In vivo analysis of Trypanosoma cruzi persistence foci at single cell resolution

Infections with Trypanosoma cruzi are usually life-long despite generating a strong adaptive immune response. Identifying the sites of parasite persistence is therefore crucial to understand how T. cruzi avoids immune-mediated destruction. However, this is a major technical challenge because the parasite burden during chronic infections is extremely low. Here, we describe an integrated approach involving comprehensive tissue processing, ex vivo imaging, and confocal microscopy, which has allowed us to visualise infected host cells in murine tissue, with exquisite sensitivity. Using bioluminescence-guided tissue sampling, with a detection level of <20 parasites, we show that in the colon, smooth muscle myocytes in the circular muscle layer are the most common infected host cell type. Typically, during chronic infections, the entire colon of a mouse contains only a few hundred parasites, often concentrated in a small number of cells containing >200 parasites, that we term mega-nests. In contrast, during the acute stage, when the total parasite burden is considerably higher and many cells are infected, nests containing >50 parasites are rarely found. In C3H/HeN mice, but not BALB/c, we identified skeletal muscle as a major site of persistence during the chronic stage, with most parasites found in large mega-nests within the muscle fibres. Finally, we report that parasites are also frequently found in the skin during chronic murine infections, often in multiple infection foci. In addition to being a site of parasite persistence, this anatomical reservoir could play an important role in insect-mediated transmission, and have implications for drug development. IMPORTANCETrypanosoma cruzi causes Chagas disease, the most important parasitic infection in Latin America. Major pathologies include severe damage to the heart and digestive tract, although symptoms do not usually appear until decades after infection. Research has been hampered by the complex nature of the disease and technical difficulties in locating the extremely low number of parasites. Here, using highly sensitive imaging technology, we reveal the sites of parasite persistence in experimental mice at single-cell resolution. We show that parasites are frequently located in smooth muscle cells in the circular muscle layer of the colon, and that skeletal muscle cells and the skin can also be important reservoirs. This information provides a framework for investigating how the parasite is able to survive as a life-long infection, despite a vigorous immune response. It also informs drug-development strategies by identifying tissue sites that must be accessed to achieve a curative outcome.

microbiology↗

bioRxiv2020

Design of an Epitope-Based Peptide Vaccine against the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): A Vaccine Informatics Approach

The recurrent and recent global outbreak of SARS-CoV-2 has turned into a global concern which has infected more than 19-million people all over the globe, and this number is increasing in hours. Unfortunate no vaccine or specific treatment is available, which make it more deadly. A vaccine-informatics approach has shown significant breakthrough in peptide-based epitope mapping and opens the new horizon in vaccine development. In this study, we have identified a total of 15 antigenic peptides (including T and B cells) in the surface glycoprotein of SARS-CoV-2 which showed non-toxic nature, non-allergenic, highly antigenic and non-mutated in other SARS-CoV-2 virus strains. The population coverage analysis has found that CD4+ T-cell peptides showed higher cumulative population coverage over to CD8+ peptides in the 16 different geographical regions of the world. We identified twelve peptides (LTDEMIAQY, WTAGAAAYY, WMESEFRVY, IRASANLAA, FGAISSVLN, VKQLSSNFG, FAMQMAYRF, FGAGAALQI, YGFQPTNGVGYQ, LPDPSKPSKR, QTQTNSPRRARS and VITPGTNTSN) that are 80% - 90% identical with experimentally determined epitopes of SARS-CoV, and this will likely be beneficial for a quick progression of the vaccine design. Moreover, docking analysis suggested that identified peptides are tightly bound in the groove of HLA molecules which can induce the T-cell response. Overall this study allows us to determine potent peptide antigen targets in surface glycoprotein on intuitive grounds which open up a new horizon in COVID-19 research. However, this study needs experimental validation by in vitro and in vivo.

bioinformatics↗

bioRxiv2020

Extensive hybridization between pig and human Ascaris identifies a highly interbred species complex infecting humans

Human ascariasis is a major neglected tropical disease caused by the nematode Ascaris lumbricoides. We report a 296 megabase (Mb) reference quality genome comprised of 17902 protein-coding genes derived from a single, representative Ascaris worm collected from 60 human hosts in Kenyan villages where pig husbandry is rare. Notably, the majority of human isolates (63/68) possessed mitochondrial genomes that clustered closer to the pig parasite Ascaris suum than to A. lumbricoides. Comparative phylogenomic analyses identified over 11 million nuclear-encoded SNPs but just two distinct genetic types that had recombined across the genomes analysed. The nuclear genomes had extensive heterozygosity and all samples existed as genetic mosaics with either A. suum-like or A. lumbricoides-like inheritance patterns supporting a highly interbred Ascaris species genetic complex. As no barriers appear to exist for anthroponotic transmission of these "hybrid" worms, a one-health approach to control the spread of human ascariasis will be necessary.

genomics↗

bioRxiv2020

Multivariate Analysis Of Potato Genotypes For Genetic Diversity

Sustainable production of food crops relies on germplasm improvement and genetic diversity that helps to identify appropriate parents, which is very important step in breeding of genotypes having high yield potential for future use. This study was conducted to investigate the extent of genetic diversity using multivariate technique on the basis of qualitative and quantitative traits. An experiment was comprised of 74 exotic genotypes and started at National Agriculture Research Center Islamabad, Pakistan during autumn 2017-2018 and 2018-2019. Data was recorded on qualitative and quantitative traits by following standard procedures and Biplot analysis was used to calculate the significance among the studied quantitative traits to exhibit the strength of relationship between traits. Results showed significant diversity in qualitative traits and quantitative traits. Red, yellowish, brown, light yellow, light brown color tubers were produced. Alike, genotypes produced yellow, cream and white flesh color tubers. Genotypes had oval, round, oblong, elliptic and reform with medium, small and large size tubers. Alike, brown, light brown, dark red and yellow eyes color was noted. In case of quantitative traits, genotypes had high variance regarding plant height, leaf area and number of tubers per lane. Genotypes had very high genetic variance for weight of tuber per plant and weight of tuber per lane while low variance was recorded for germination, number of stem per plant and number of eyes per tuber. Significant positive correlation was observed between number of tubers per plant (TPP) with number of eyes on tubers (r = 0.241) and number of tubers per lane (TPL) (r = 0.349). But negative correlation was noted between number of tubers per plant (TPP) with plant height (r = - 246), leaf area (-0.529) and germination (r = -0.283). Plant height was found significantly positive correlated with leaf area (r= 0.456), germination percentage (r = 0.255) and weight of tubers per plant (r = 0.307). Leaf area (LA) showed positive significant correlation with number of tubers per plant (r = 0.466) and weight of tubers per plant (r = 0.263)., yield and harvest index (r = 0.798, 0.755, 0.255). Weight of tubers per lane (WTL) showed positive correlation with weight of tubers per plant (r = 0.387). Regarding the interrelation between the traits and genotypes, the first two principal component axes (PC1, 24.83% and PC2, 23.46%) accounted for about 48.29% of the total variability reflecting the complexity of the variation between the plotted traits of genotypes.

genetics↗

bioRxiv2020

Evaluating features of scientific conferences: A call for improvements

Scientific conferences provide valuable opportunities for researchers across career stages and disciplines to present their latest work, and to network with their peers. These meetings have largely been held in-person with rapid proliferation in the number of meetings and attendees. Yet the format and quality of their organization lag behind what is possible and as a result, the current experience of attending conferences in many disciplines remains unchanged in many respects. We created a database of 270 national and international academic conferences held in-person during 2018-2019 in various disciplines and examined them for their features, costs and impact on the community. We found that many meetings could still be improved significantly in terms of diversity, inclusivity, promoting early career researcher (ECR) networking and career development, venue accessibility, and importantly, reducing the meetings carbon footprint. It is important to accelerate and mandate efforts to improve conferences so that researchers in all disciplines, in particular ECRs, consistently benefit from scientific gatherings, for years to come. We discuss a combination of approaches and recommendations to make conferences more modern, effective, equitable and intellectually productive for the research community and environmentally sustainable for our planet. "They always say time changes things, but you actually have to change them yourself." -- Andy Warhol

scientific communication and education↗

bioRxiv2020

Computational vaccinology based development of multi-epitope subunit vaccine for protection against the Norovirus infections

Human Norovirus belong to family Calciviridae, it was identified in the outbreak of gastroenteritis in Norwalk, due to its seasonal prevalence known as "winter vomiting disease". Treatment of Norovirus infection is still mysterious because there is no effective antiviral drugs or vaccine developed to protect against the infection, to eradicate the infection an effective vaccine should be developed. In this study capsid protein (A7YK10), small protein (A7YK11) and polyprotein (A7YK09) were utilized. These proteins were subjected to B and T cell epitopes prediction by using reliable immunoinformatics tools. The antigenic and non-allergenic epitopes were selected for subunit vaccine, which can activate cellular and humoral immune responses. Linkers joined these epitopes together. The vaccine structure was modelled and validated by using Errat, ProSA and rampage servers. The modelled vaccine was docked with TLR-7. Stability of the docked complex was evaluated by MD simulation. In order to apply the concept in a wet lab, the reverse translated vaccine sequence was cloned in pET28a (+). The vaccine developed in this study requires experimental validation to ensure its effectiveness against the disease.

immunology↗

bioRxiv2020

Loss of α2-6 sialylation promotes the transformation of synovial fibroblasts into a pro-inflammatory phenotype in Rheumatoid Arthritis.

In healthy joints, synovial fibroblasts (SFs) provide the microenvironment required to mediate homeostasis but are recognized to adopt a pathological role in rheumatoid arthritis (RA), promoting the infiltration and activation of immune cells to perpetuate local inflammation, pain and joint destruction. Carbohydrates (glycans) attached to cell surface proteins are fundamental regulators of cellular interactions between stromal and immune cells, but very little is known about the glycome of SFs or how glycosylation regulates their biology. Here we fill these gaps in our understanding of stromal guided pathophysiology by systematically mapping glycosylation pathways in healthy and arthritic SFs. We used a combination of transcriptomic and glycomic analysis to show that transformation of fibroblasts into pro-inflammatory cells in RA is associated with profound glycan remodeling, a process that involves reduction of 2-6 terminal sialylation that is mostly mediated by TNF-dependent inhibition of the glycosyltransferase ST6Gal1. We also show that sialylation of SFs correlates with distinct disease stages and SFs functional subsets in both human RA and models of mouse arthritis. We propose that pro-inflammatory cytokines in the joint remodel the SF-glycome, transforming a regulatory tissue intended to preserve local homeostasis, into an under-sialylated and highly pro-inflammatory microenvironment that contributes to an amplificatory inflammatory network that perpetuates chronic inflammation. These results highlight the importance of cell glycosylation in stromal immunology.

immunology↗

bioRxiv2020

The Vpu-interacting protein ATP6V0C regulates expression of tetherin and HIV-1 release

The HIV-1 accessory protein Vpu enhances virus release by down-regulating cell surface expression of the host restriction factor tetherin. To further understand the role of host proteins in Vpu function, we carried out yeast two-hybrid screening and identified the V0 subunit C of vacuolar ATPase (ATP6V0C) as a Vpu-binding protein. To examine the role of ATP6V0C in Vpu-mediated tetherin degradation and HIV-1 release, we knocked down ATP6V0C expression in HeLa cells and observed that ATP6V0C depletion impairs Vpu-mediated tetherin degradation, resulting in a defect in HIV-1 release. We also observed that overexpression of ATP6V0C stabilizes tetherin expression. This stabilization is specific to ATP6V0C, as overexpression of another subunit of the vacuolar ATPase, ATP6V0C", had no effect on tetherin expression. ATP6V0C overexpression did not stabilize CD4, another target of Vpu-mediated degradation. Immunofluorescence localization studies showed that the ATP6V0C-stabilized tetherin is sequestered in a CD63- and LAMP1-positive intracellular compartment. These data demonstrate that the Vpu-interacting protein ATP6V0C plays a role in regulating tetherin expression and HIV-1 assembly and release.

microbiology↗

bioRxiv2019

Cell-type specificity of neuronal excitability and morphology in the central amygdala

Central amygdala (CeA) neurons expressing protein kinase C delta (PKC{delta}+) or Somatostatin (Som+) differentially modulate diverse behaviors. The underlying features supporting cell-type-specific function in the CeA, however, remain unknown. Using whole-cell patch-clamp electrophysiology in acute mouse brain slices and biocytin-based neuronal reconstructions, we demonstrate that neuronal morphology and relative excitability are two distinguishing features between Som+ and PKC{delta}+ CeLC neurons. Som+ neurons, for example, are more excitable, compact and with more complex dendritic arborizations than PKC{delta}+ neurons. Cell size, intrinsic membrane properties, and anatomical localization were further shown to correlate with cell-type-specific differences in excitability. Lastly, in the context of neuropathic pain, we show a shift in the excitability equilibrium between PKC{delta}+ and Som+ neurons, suggesting that imbalances in the relative output of these cells underlie maladaptive changes in behaviors. Together, our results identify fundamentally important distinguishing features of PKC{delta}+ and Som+ cells that support cell-type-specific function in the CeA.

neuroscience↗

bioRxiv2019

Assessing white matter pathway reproducibility from human whole-brain tractography clustering

Diffusion MRI, together with tractography techniques, is a non-invasive tool to investigate the brains structural pathways (tracts). These tracts join together different regions of the brain and tract identification often involves the use of manual ROIs or automated techniques such as clustering. By studying these connections, current understanding of the connectome can be improved and changes due to disease in patient populations may be identified. We developed a tool to automatically identify all pathways in the human brain, including the short-range, U-shaped tracts, and map quantitative scalar metrics along the pathway trajectory for subsequent analysis. Pathways are identified via a spectral clustering technique on two datasets: Human Connectome Project (intersubject) and MyConnectome Project (intrasubject) and the reliability of the extracted tract and scalar values are evaluated. Average Euclidean distances and volumetric overlap were computed and indicated good spatial reliability. Intraclass correlations of the fractional anisotropy value mapped along the tract was calculated and exhibited good reproducibility within each dataset. Additionally, these evaluation metrics, together with the coefficient of variation of the mean streamline count is used to determine reliably identified U-shaped tracts across the datasets. The developed tract identification tool is an additional resource to studying the human connectome with increased confidence in the results. The identified reliable U-shaped tracts contributes to the identification of common structural connections across individuals and aids in advancing our understanding of the brains short-range pathways.

bioinformatics↗

bioRxiv2019

Breeding behaviour and productivity of Black-necked crane (Grus nigricolis) in Ladakh, Indian Trans-Himalaya

A long-term study was conducted to understand some aspects of breeding biology of Black-necked crane (Grus nigricollis) in Changthang, Ladakh. Data on aspects such as the breeding season, courtship, mating, egg laying and incubation period, nest site fidelity, egg morphometry, breeding productivity and recruitment rate were collected between 2003 and 2012. Black-necked crane started arriving from last week of March to first half of April and showed fidelity at ten nesting sites. Courtship and mating peaked early morning (0700 hours), around noon (1100 hours) and in late evening (0600 hours) while the nest building at evening (1600 hours). The egg laying period initiated in May and extended up to July. The average incubation period was 33.88{+/-}0.3 days. Hatching success, nest survival rate and fledgling increment rate of the bird were 73.3%, 0.55 {+/-} 0.03 and 0.41 {+/-} 0.02 respectively with an overall breeding productivity of 0.73. The present population of Black-necked crane in Changthang, Ladakh seems to stable with an average recruitment rate of 15.7{+/-}1.4.

ecology↗

bioRxiv2019

New North American isolates of Venturia inaequalis can overcome apple scab resistance of Malus floribunda 821

Apple scab, caused by Venturia inaequalis (Cke.) Wint., is a destructive fungal disease of major apple cultivars worldwide, most of which are moderately to highly susceptible. Thus, development of scab resistant cultivars is one of the highest priorities of apple breeding programs. The principal source of resistance for breeding programs has been the scab resistance gene Rvi6 that originated from the Japanese crabapple Malus floribunda (Sieb.) sel. 821. Isolates of V. inaequalis able to overcome Rvi6 have been identified in Europe, but have not yet been reported on the American continents. We recently discovered scab infection on M. floribunda 821 trees in a research orchard at Geneva, New York, USA, where approximately 10% of the leaves bore profusely sporulating apple scab lesions, many of which had coalesced to cover entire leaves. Chlorosis and pinpoint pitting symptoms typical of failed infections by V. inaequalis on hosts bearing the Rvi6 and Rvi7 genes were also observed. We assessed genetic diversity and population genetic structure of six V. inaequalis isolates collected from M. floribunda 821, one isolate from Nova Easygro, one isolate from Golden Delicious and two isolates from Europe (11 isolates in total) using 16,321 genome-wide SNPs. Population genetic structure and PCA separated the isolates into distinct European and USA groups. The forgoing suggests that the new Rvi6 virulent isolates emerged within USA populations, rather than being transported from Europe. The overcoming of resistance in M. floribunda 821 but not in descendant cultivars suggests that durable resistance to apple scab will require a more comprehensive understanding of Rvi6 mediated resistance in diverse genetic backgrounds.

pathology↗

bioRxiv2019

Overnight caloric restriction prior to cardiac arrest and resuscitation leads to improved survival and neurological outcome in a rodent model

While interest toward caloric restriction (CR) in various models of brain injury has increased in recent decades, studies have predominantly focused on the benefits of chronic or intermittent CR. The effects of ultra-short, including overnight, CR on acute ischemic brain injury, however, are not well studied. Here, we show that overnight caloric restriction (75% over 14 h) prior to asphyxial cardiac arrest and resuscitation (CA) improves survival and neurological recovery, including complete prevention of neurodegeneration in multiple regions of the brain. We also show that overnight CR normalizes stress-induced hyperglycemia, while significantly decreasing insulin and glucagon production and increasing corticosterone and ketone body production. The benefits seen with ultra-short CR appear independent of Sirtuin 1 (SIRT-1) and brain-derived neurotrophic factor (BDNF) expression, which have been strongly linked to neuroprotective benefits seen in chronic CR. Further exploration into the precise mechanisms involved in ultra-short CR may have significant translational implications. These findings are also of importance to basic sciences research as we demonstrate that minor, often-overlooked alterations to pre-experimental dietary procedures can significantly affect results, and by extension, research homogeneity and reproducibility, especially in acute ischemic brain injury models.

neuroscience↗