Prototyping a wearable and stretchable graphene-on-PDMS sensor for strain detection on human body physiological and joint movements.

In the era of wearable electronic devices, which are quite popular nowadays, our research is focused on flexible as well as stretchable strain sensors, which are gaining humongous popularity because of recent advances in nanocomposites and their microstructures. Sensors that are stretchable and flexible based on graphene can be a prospective 'gateway' over the considerable biomedical speciality. The scientific community still faces a great problem in developing versatile and user-friendly graphene-based wearable strain sensors that satisfy the prerequisites of susceptible, ample range of sensing, and recoverable structural deformations. In this paper, we report the fabrication, development, detailed experimental analysis and electronic interfacing of a robust but simple PDMS/graphene/PDMS (PGP) multilayer strain sensor by drop casting conductive graphene ink as the sensing material onto a PDMS substrate. Electrochemical exfoliation of graphite leads to the production of abundant, fast and economical graphene. The PGP sensor selective to strain has a broad strain range of ⁓60%, with a maximum gauge factor of 850, detection of human physiological motion and personalized health monitoring, and the versatility to detect stretching with great sensitivity, recovery and repeatability. Additionally, recoverable structural deformation is demonstrated by the PGP strain sensors, and the sensor response is quite rapid for various ranges of frequency disturbances. The structural designation of graphene's overlap and crack structure is responsible for the resistance variations that give rise to the remarkable strain detection properties of this sensor. The comprehensive detection of resistance change resulting from different human body joints and physiological movements demonstrates that the PGP strain sensor is an effective choice for advanced biomedical and therapeutic electronic device utility.

ATAV: a comprehensive platform for population-scale genomic analyses.

BACKGROUND: A common approach for sequencing studies is to do joint-calling and store variants of all samples in a single file. If new samples are continually added or controls are re-used for several studies, the cost and time required to perform joint-calling for each analysis can become prohibitive. RESULTS: We present ATAV, an analysis platform for large-scale whole-exome and whole-genome sequencing projects. ATAV stores variant and per site coverage data for all samples in a centralized database, which is efficiently queried by ATAV to support diagnostic analyses for trios and singletons, as well as rare-variant collapsing analyses for finding disease associations in complex diseases. Runtime logs ensure full reproducibility and the modularized ATAV framework makes it extensible to continuous development. Besides helping with the identification of disease-causing variants for a range of diseases, ATAV has also enabled the discovery of disease-genes by rare-variant collapsing on datasets containing more than 20,000 samples. Analyses to date have been performed on data of more than 110,000 individuals demonstrating the scalability of the framework. To allow users to easily access variant-level data directly from the database, we provide a web-based interface, the ATAV data browser ( http://atavdb.org/ ). Through this browser, summary-level data for more than 40,000 samples can be queried by the general public representing a mix of cases and controls of diverse ancestries. Users have access to phenotype categories of variant carriers, as well as predicted ancestry, gender, and quality metrics. In contrast to many other platforms, the data browser is able to show data of newly-added samples in real-time and therefore evolves rapidly as more and more samples are sequenced. CONCLUSIONS: Through ATAV, users have public access to one of the largest variant databases for patients sequenced at a tertiary care center and can look up any genes or variants of interest. Additionally, since the entire code is freely available on GitHub, ATAV can easily be deployed by other groups that wish to build their own platform, database, and user interface.

Genome-wide functional annotation of dual-specificity protein- and lipid-binding modules that regulate protein interactions.

Emerging evidence indicates that membrane lipids regulate protein networking by directly interacting with protein-interaction domains (PIDs). As a pilot study to identify and functionally annodate lipid-binding PIDs on a genomic scale, we performed experimental and computational studies of PDZ domains. Characterization of 70 PDZ domains showed that ~40% had submicromolar membrane affinity. Using a computational model built from these data, we predicted the membrane-binding properties of 2,000 PDZ domains from 20 species. The accuracy of the prediction was experimentally validated for 26 PDZ domains. We also subdivided lipid-binding PDZ domains into three classes based on the interplay between membrane- and protein-binding sites. For different classes of PDZ domains, lipid binding regulates their protein interactions by different mechanisms. Functional studies of a PDZ domain protein, rhophilin 2, suggest that all classes of lipid-binding PDZ domains serve as genuine dual-specificity modules regulating protein interactions at the membrane under physiological conditions.

Enhancing the Immune Response of a Nicotine Vaccine with Synthetic Small "Non-Natural" Peptides.

The addictive nature of nicotine is likely the most significant reason for the continued prevalence of tobacco smoking despite the widespread reports of its negative health effects. Nicotine vaccines are an alternative to the currently available smoking cessation treatments, which have limited efficacy. However, the nicotine hapten is non-immunogenic, and successful vaccine formulations to treat nicotine addiction require both effective adjuvants and delivery systems. The immunomodulatory properties of short, non-natural peptide sequences not found in human systems and their ability to improve vaccine efficacy continue to be reported. The aim of this study was to determine if small "non-natural peptides," as part of a conjugate nicotine vaccine, could improve immune responses. Four peptides were synthesized via solid phase methodology, purified, and characterized. Ex vivo plasma stability studies using RP-HPLC confirmed that the peptides were not subject to proteolytic degradation. The peptides were formulated into conjugate nicotine vaccine candidates along with a bacterial derived adjuvant vaccine delivery system and chitosan as a stabilizing compound. Formulations were tested in vitro in a dendritic cell line to determine the combination that would elicit the greatest 1L-1ß response using ELISAs. Three of the peptides were able to enhance the cytokine response above that induced by the adjuvant delivery system alone. In vivo vaccination studies in BALB/c mice demonstrated that the best immune response, as measured by nicotine-specific antibody levels, was elicited from the conjugate vaccine structure, which included the peptide, as well as the other components. Isotype analyses highlighted that the peptide was able to shift immune response toward being more humorally dominant. Overall, the results have implications for the use of non-natural peptides as adjuvants not only for the development of a nicotine vaccine but also for use with other addictive substances and conventional vaccination targets as well.

C-reactive protein as a prognostic marker of Plasmodiumfalciparum malaria severity.

BACKGROUND & OBJECTIVES: Plasmodiumfalciparum malaria causes wide variety of clinical symptoms ranging from a mild febrile illness to life-threatening complications. For prevention of the severity and early diagnosis, evaluation of potential biomarkers is much needed. C-reactive protein (CRP) is an acute phase protein and well-recognized marker of inflammation in the body. It is synthesized by liver in response to pro-inflammatory responses and has correlation with complications associated with malaria. The study was aimed to assess, if it could serve as a predictive marker for malaria disease severity. METHODS: In the present study, 74 P. falciparum patients and 22 healthy controls were enrolled. Turbidimetric immunoassay was used to measure the CRP in serum samples of all the study participants. Mann-Whitney U-test for continuous data and chi-square test for categorical data were used to compare all malaria cases vs. healthy control group and uncomplicated vs. severe malaria groups. Using receiver operating characteristic (ROC) analysis, best threshold value was determined for CRP in severe malaria patients. RESULTS: CRP level was significantly elevated in all malaria case groups (1.6 mg/dl IQ 1-2.6) as compared to healthy controls (0.10 mg/dl IQ 0.1-0.20), with p-value <0.0001. Further, CRP level was significantly higher in the severe malaria group (2 mg/dl IQ 1.8-3.9) as compared to the uncomplicated malaria group (1.4 mg/dl IQ 1-2.47) and healthy control group (0.10 mg/dl IQ 0.10-0.20), with p-value <0.05. INTERPRETATION & CONCLUSION: The present study findings suggest that CRP level can be used to differentiate severe malaria from uncomplicated malaria. Elevated CRP level could be helpful in early prediction of the disease severity in patients infected with P. falciparum and may play an important role in diagnosis of falciparum malaria where improper initial test and clinical manifestations like fever may be absent even with a high load of parasite.

Architecture of the human regulatory network derived from ENCODE data.

Transcription factors bind in a combinatorial fashion to specify the on-and-off states of genes; the ensemble of these binding events forms a regulatory network, constituting the wiring diagram for a cell. To examine the principles of the human transcriptional regulatory network, we determined the genomic binding information of 119 transcription-related factors in over 450 distinct experiments. We found the combinatorial, co-association of transcription factors to be highly context specific: distinct combinations of factors bind at specific genomic locations. In particular, there are significant differences in the binding proximal and distal to genes. We organized all the transcription factor binding into a hierarchy and integrated it with other genomic information (for example, microRNA regulation), forming a dense meta-network. Factors at different levels have different properties; for instance, top-level transcription factors more strongly influence expression and middle-level ones co-regulate targets to mitigate information-flow bottlenecks. Moreover, these co-regulations give rise to many enriched network motifs (for example, noise-buffering feed-forward loops). Finally, more connected network components are under stronger selection and exhibit a greater degree of allele-specific activity (that is, differential binding to the two parental alleles). The regulatory information obtained in this study will be crucial for interpreting personal genome sequences and understanding basic principles of human biology and disease.

Low holo-transcobalamin levels are prevalent in vegetarians and is associated with coronary artery disease in Indian population.

Coronary artery disease (CAD) has been increasing alarmingly in India. We had earlier shown that vitamin B12 deficiency is associated with CAD in Indian population. However, only about a quarter of the total vitamin B12 is internalised in the cells by the proteins transcobalamin II. Vitamin B12-bound transcobalamin II (holotranscobalamin, holoTC) is thus referred to as biologically active B12. In this study, we ascertained the levels of holoTC in 501 CAD cases and 1253 healthy controls and for the first time show that holoTC levels are significantly lower (p = 2.57E-4) in CAD (26.81 pmol/l) cases as compared to controls (29.97 pmol/l).

Diverse roles and interactions of the SWI/SNF chromatin remodeling complex revealed using global approaches.

A systems understanding of nuclear organization and events is critical for determining how cells divide, differentiate, and respond to stimuli and for identifying the causes of diseases. Chromatin remodeling complexes such as SWI/SNF have been implicated in a wide variety of cellular processes including gene expression, nuclear organization, centromere function, and chromosomal stability, and mutations in SWI/SNF components have been linked to several types of cancer. To better understand the biological processes in which chromatin remodeling proteins participate, we globally mapped binding regions for several components of the SWI/SNF complex throughout the human genome using ChIP-Seq. SWI/SNF components were found to lie near regulatory elements integral to transcription (e.g. 5' ends, RNA Polymerases II and III, and enhancers) as well as regions critical for chromosome organization (e.g. CTCF, lamins, and DNA replication origins). Interestingly we also find that certain configurations of SWI/SNF subunits are associated with transcripts that have higher levels of expression, whereas other configurations of SWI/SNF factors are associated with transcripts that have lower levels of expression. To further elucidate the association of SWI/SNF subunits with each other as well as with other nuclear proteins, we also analyzed SWI/SNF immunoprecipitated complexes by mass spectrometry. Individual SWI/SNF factors are associated with their own family members, as well as with cellular constituents such as nuclear matrix proteins, key transcription factors, and centromere components, implying a ubiquitous role in gene regulation and nuclear function. We find an overrepresentation of both SWI/SNF-associated regions and proteins in cell cycle and chromosome organization. Taken together the results from our ChIP and immunoprecipitation experiments suggest that SWI/SNF facilitates gene regulation and genome function more broadly and through a greater diversity of interactions than previously appreciated.

Selective elimination of younger erythrocytes in blood circulation and associated molecular changes in benzo (a) pyrene induced mouse model of lung cancer.

Background: Anemia is a common feature in cancer patients. The present research was conducted to explore the mechanisms of induction of anemia in a mouse model of lung cancer. Methods: The lung cancer was induced by treating orally with BaP (50 mg/kg body weight, twice a week for four weeks). The erythrocyte kinetics were studied using a double in vivo biotinylation (DIB) technique. ROS production and apoptosis analysis were done by staining with the CMH2DCFDA stain and anti-mouse Annexin V antibody, followed by flow cytometry. The expression of antioxidant, apoptotic, anti-apoptotic and inflammatory genes was analyzed by quantitative PCR (RT-qPCR). Results: BaP-induced tumour reduced body weight and induced persistent haemolytic anaemia. The kinetics data suggest that, though reticulocyte production was enhanced, the proportion of young erythrocytes did not increase in the same proportion. The young aged erythrocytes were selectively eliminated from blood circulation, but intermediate and old aged erythrocytes persisted for a longer duration. The tumour progression leads to a significant increase in ROS production and apoptosis in the erythrocytes. The molecular data suggests that the expression levels of antioxidants (SOD1, catalase, and GPX1) and erythropoietin (Epo) were significantly increased. The anti-inflammatory genes Interleukin-6 (IL-6), Interleukin-10 (IL-10) were significantly decreased.Apoptotic genes Bax, and caspase 3 were significantly decreased while Bcl 2 was significantly increased in the blood of tumour-bearing mice. Conclusions: The overall data suggest that erythrocyte turnover is severely modulated with the progression of tumor. The apoptosis, ROS levels, antioxidant, anti-apoptotic, and Epo gene expressions were increased, but proapoptotic and anti-inflammatory gene expression were suppressed.

Aflatoxin B1 administration causes inflammation and apoptosis in the lungs and spleen.

Aflatoxin is a naturally occurring mycotoxin that has numerous toxic effects. The main aim of the present study was to evaluate the toxic effects of aflatoxin B1 (AFB1) on the lungs and spleen. Mice were repeatedly exposed to AFB1 (0.3 mg/kg body weight) on alternate days for four weeks via oral route. The histopathological data in AFB1-treated mice show alveolar epithelial hyperplasia with inflammation and the presence of numerous alveolar macrophages with minimal hemorrhage. There was an increase in vascular neutrophils and interstitial inflammation. The branching of vessels was plugged with neutrophils. AFB1 administration also causes splenomegaly. The AFB1-treated spleen shows the tingible body macrophages (TBM) scattered within the splenic white pulp. Apoptosis may lead to atrophy in a selected region of the white pulp area. There is a decrease in cellularity within the periarteriolar lymphatic sheath (PALS). The inflammation causes the congestion of red pulp with the increase in nuclear debris, and vacuoles are also visible. The flow cytometry data further suggests enhanced apoptosis in lung and spleen cells.

Impact of sphingolipid synthesis inhibition on the drug susceptibility patterns of Trichophyton species.

The well known dermatophyte infections caused by Trichophyton species are an ambiguous problem to treat using the present arsenal of antifungals. This study expounds on the effect of inhibition of sphingolipid pathway on Trichophyton growth. Findings from the drug susceptibility assays suggest sphingolipid inhibition severely restricts the growth of T. interdigitale and T. tonsurans. The observed synergistic effects of combinations of sphingolipid inhibitor and conventional drugs provide a promising treatment strategy against Trichophyton infection.

Multifaceted Spindle Cell/Sclerosing Rhabdomyosarcoma With Role of Immunohistochemistry in Avoiding Misdiagnosis: A Multi-Institutional Study of 45 Distinct Tumors.

Background. Spindle cell/sclerosing rhabdomyosarcoma is a rare neoplasm and has an aggressive clinical course. Because of its rarity, we performed a multi-institutional collaboration to comprehend the overarching clinical, histopathological, and immunohistochemical characteristics of a cohort of spindle cell/sclerosing rhabdomyosarcoma. Materials and Methods. Forty-five patients with spindle cell/sclerosing rhabdomyosarcoma were identified. Demographics, clinical, histopathological, and immunohistochemistry data were reviewed and recorded. Results. The patients' age ranged from 1 to 85 years with a male to female ratio of 1.2:1. There were 15 children/adolescents and 30 adults. Eighteen (40%) tumors were located in the head and neck region. Twenty-four (53%) tumors displayed a bimorphic cellular arrangement with hypercellular areas having short, long, and sweeping fascicular and herringbone pattern, and hypocellular areas with stromal sclerosis and associated hyalinized and/or chondromyxoid matrix. Histomorphological differentials considered were leiomyosarcoma, malignant peripheral nerve sheath tumor, fibrosarcoma, nodular fasciitis, liposarcoma, synovial sarcoma, sarcomatoid carcinoma, solitary fibrous tumor, dermatofibrosarcoma protuberans, and schwannoma. Six tumors exhibited marked stromal sclerosis. The myogenic nature was confirmed by immunohistochemistry. Positivity for at least one skeletal muscle-associated marker (MyoD1 and/or myogenin) was observed. Conclusion. Spindle cell/sclerosing rhabdomyosarcoma diagnosis can be challenging as a number of malignant spindle cell neoplasm mimic this entity. Thus a correct diagnosis requires immunohistochemical work up with a broad panel of antibodies. In view of rarity of this neoplasm, further studies on a large cohort of patients with clinical follow-up data are needed for a better understanding of this tumor.

Evaluation of programmed cell death ligand 1 expression in a contemporary cohort of penile squamous cell carcinoma and its correlation with clinicopathologic and survival parameters: A study of 134 patients.

OBJECTIVES: Penile squamous cell carcinomas (PCs) are rare malignancies with a dismal prognosis in a metastatic setting; therefore, novel immunotherapeutic modalities are an unmet need. One such modality is the immune checkpoint molecule programmed cell death ligand 1 (PD-L1). We sought to analyze PD-L1 expression and its correlation with various clinicopathologic parameters in a contemporary cohort of 134 patients with PC. METHODS: A cohort of 134 patients with PC was studied for PD-L1 immunohistochemistry. The PD-L1 expression was evaluated using a combined proportion score with a cutoff of 1 or higher to define positivity. The results were correlated with various clinicopathologic parameters. RESULTS: Overall, 77 (57%) patients had positive PD-L1 expression. Significantly high PD-L1 expression was observed in high-grade tumors (P = .006). We found that 37% of human papillomavirus (HPV)-associated subtypes and 73% of other histotype tumors expressed PD-L1, while 63% of HPV-associated tumors and 27% of other histotype tumors did not (odds ratio, 1.35; P = .002 when compared for HPV-associated groups vs all others). Similarly, PD-L1-positive tumors had a 3.61-times higher chance of being node positive than PD-L1-negative tumors (P = .0009). In addition, PD-L1 high-positive tumors had a 5-times higher chance of being p16ink4a negative than PD-L1 low-positive tumors (P = .004). The PD-L1-positive tumors had a lower overall survival and cancer-specific survival than PD-L1-negative tumors. CONCLUSIONS: Overall, PD-L1 expression is associated with high-grade and metastatic tumors. Lower PD-L1 expression is observed more frequently in HPV-associated (warty or basaloid) subtypes than in other, predominantly HPV-independent types. As a result, PD-L1 positivity, including higher expression, portends lower overall and cancer-specific survival. These data provide a rational for further investigating PD-L1-based immunotherapeutics in PC.

The molecular basis of ceramide-1-phosphate recognition by C2 domains.

Group IVA cytosolic phospholipase A2 (cPLA2α), which harbors an N-terminal lipid binding C2 domain and a C-terminal lipase domain, produces arachidonic acid from the sn-2 position of zwitterionic lipids such as phosphatidylcholine. The C2 domain has been shown to bind zwitterionic lipids, but more recently, the anionic phosphomonoester sphingolipid metabolite ceramide-1-phosphate (C1P) has emerged as a potent bioactive lipid with high affinity for a cationic patch in the C2 domain ß-groove. To systematically analyze the role that C1P plays in promoting the binding of cPLA2α-C2 to biological membranes, we employed biophysical measurements and cellular translocation studies along with mutagenesis. Biophysical and cellular translocation studies demonstrate that C1P specificity is mediated by Arg59, Arg6¹, and His6² (an RxRH sequence) in the C2 domain. Computational studies using molecular dynamics simulations confirm the origin of C1P specificity, which results in a spatial shift of the C2 domain upon membrane docking to coordinate the small C1P headgroup. Additionally, the hydroxyl group on the sphingosine backbone plays an important role in the interaction with the C2 domain, further demonstrating the selectivity of the C2 domain for C1P over phosphatidic acid. Taken together, this is the first study demonstrating the molecular origin of C1P recognition.

A structure-based protocol for learning the family-specific mechanisms of membrane-binding domains.

MOTIVATION: Peripheral membrane-targeting domain (MTD) families, such as C1-, C2- and PH domains, play a key role in signal transduction and membrane trafficking by dynamically translocating their parent proteins to specific plasma membranes when changes in lipid composition occur. It is, however, difficult to determine the subset of domains within families displaying this property, as sequence motifs signifying the membrane binding properties are not well defined. For this reason, procedures based on sequence similarity alone are often insufficient in computational identification of MTDs within families (yielding less than 65% accuracy even with a sequence identity of 70%). RESULTS: We present a machine learning protocol for determining membrane-targeting properties achieving 85-90% accuracy in separating binding and non-binding domains within families. Our model is based on features from both sequence and structure, thereby incorporation statistics obtained from the entire domain family and domain-specific physical quantities such as surface electrostatics. In addition, by using the enriched rules in alternating decision tree classifiers, we are able to determine the meaning of the assigned function labels in terms of biological mechanisms. CONCLUSIONS: The high accuracy of the learned models and good agreement between the rules discovered using the ADtree classifier and mechanisms reported in the literature reflect the value of machine learning protocols in both prediction and biological knowledge discovery. Our protocol can thus potentially be used as a general function annotation and knowledge mining tool for other protein domains. AVAILABILITY: metador.bioengr.uic.edu CONTACT: huilu@uic.edu.

Analysis of diverse regulatory networks in a hierarchical context shows consistent tendencies for collaboration in the middle levels.

Gene regulatory networks have been shown to share some common aspects with commonplace social governance structures. Thus, we can get some intuition into their organization by arranging them into well-known hierarchical layouts. These hierarchies, in turn, can be placed between the extremes of autocracies, with well-defined levels and clear chains of command, and democracies, without such defined levels and with more co-regulatory partnerships between regulators. In general, the presence of partnerships decreases the variation in information flow amongst nodes within a level, more evenly distributing stress. Here we study various regulatory networks (transcriptional, modification, and phosphorylation) for five diverse species, Escherichia coli to human. We specify three levels of regulators--top, middle, and bottom--which collectively govern the non-regulator targets lying in the lowest fourth level. We define quantities for nodes, levels, and entire networks that measure their degree of collaboration and autocratic vs. democratic character. We show individual regulators have a range of partnership tendencies: Some regulate their targets in combination with other regulators in local instantiations of democratic structure, whereas others regulate mostly in isolation, in more autocratic fashion. Overall, we show that in all networks studied the middle level has the highest collaborative propensity and coregulatory partnerships occur most frequently amongst midlevel regulators, an observation that has parallels in corporate settings where middle managers must interact most to ensure organizational effectiveness. There is, however, one notable difference between networks in different species: The amount of collaborative regulation and democratic character increases markedly with overall genomic complexity.

Comparing genomes to computer operating systems in terms of the topology and evolution of their regulatory control networks.

The genome has often been called the operating system (OS) for a living organism. A computer OS is described by a regulatory control network termed the call graph, which is analogous to the transcriptional regulatory network in a cell. To apply our firsthand knowledge of the architecture of software systems to understand cellular design principles, we present a comparison between the transcriptional regulatory network of a well-studied bacterium (Escherichia coli) and the call graph of a canonical OS (Linux) in terms of topology and evolution. We show that both networks have a fundamentally hierarchical layout, but there is a key difference: The transcriptional regulatory network possesses a few global regulators at the top and many targets at the bottom; conversely, the call graph has many regulators controlling a small set of generic functions. This top-heavy organization leads to highly overlapping functional modules in the call graph, in contrast to the relatively independent modules in the regulatory network. We further develop a way to measure evolutionary rates comparably between the two networks and explain this difference in terms of network evolution. The process of biological evolution via random mutation and subsequent selection tightly constrains the evolution of regulatory network hubs. The call graph, however, exhibits rapid evolution of its highly connected generic components, made possible by designers' continual fine-tuning. These findings stem from the design principles of the two systems: robustness for biological systems and cost effectiveness (reuse) for software systems.

Aflatoxin B1 administration induces reactive oxygen species production and apoptosis of erythrocytes in mice.

Aflatoxin is a naturally occurring mycotoxin that has various toxic effects to humans and various other animals. In the current study, we have investigated the toxic effects of Aflatoxin B1 (AFB1) on erythrocytes in the blood circulation of mice. Mice were administered orally with repeated doses of AFB1 (0.3 mg/kg of body weight three times a week for four weeks). AFB1 administration resulted in sustained anemia and a significant reduction in blood erythrocyte number as well as hemoglobin level was seen at different time schedules. Body weight, erythrocyte count, and Hb were significantly decreased on days 30 and 45 post-AFB1 administration. The reticulocytes proportion in circulation was analyzed by staining the cells with anti-mouse CD71 monoclonal antibody and flow cytometric analysis. The ROS level and apoptotic cell proportion were determined by staining with CM-H2DCFDA and Annexin V antibody. AFB1 treatment leads to an increment in reticulocytes production. A significant increase in reactive oxygen species (ROS) and apoptotic cells were also observed in erythrocytes.

Altered dynamics of mitochondria and reactive oxygen species in the erythrocytes of migrating red-headed buntings.

Background: Blood antioxidants provide propensity to mitigate reactive oxygen species (ROS) apart from other oxidative challenges during a high-energy state of migration in night migratory songbirds. The study investigated the modulation of erythrocytes, mitochondrial abundance, hematocrit changes, and relative expression of fat transport-related genes during migration in red-headed buntings (Emberiza bruniceps). We hypothesized an increase in antioxidants along with the mitigation of mitochondria-related reactive oxygen species elevation and consequential apoptosis occurring during migration. Methods: Male red-headed buntings (n = 6) were placed under short days (8 h of light and 16 h of dark, 8L:16D)/long days (14L:10D) and photo induced to simulated non-migratory, nMig; pre-migratory, pMig; and migratory, Mig, states. Erythrocyte shape, reactive oxygen species production, mitochondrial membrane potential (MMP), reticulocyte proportion, and apoptosis were analyzed using flow cytometry and relative expression of fat metabolizing and antioxidant genes was measured by using qPCR. Results: There was a significant increase in hematocrit, erythrocyte area, and mitochondrial membrane potential. Reactive oxygen species and apoptotic erythrocyte proportion declined in the Mig state. The changes in antioxidant genes (SOD1 and NOS2), fatty acid translocase (CD36), and metabolic (FABP3, DGAT2, GOT2, and ATGL) genes showed a significant increment during the Mig state. Conclusion: These results suggested that adaptive changes occur in mitochondrial behavior and apoptosis of erythrocytes. The transition in erythrocytes, antioxidant genes, and fatty acid metabolism gene expressions suggested differences in regulatory strategies at the cellular/transcriptional level during different states of simulated migration in birds.

Beyond membrane components: uncovering the intriguing world of fungal sphingolipid synthesis and regulation.

Sphingolipids (SLs) are essential to fungal survival and represent a major class of structural and signaling lipids. Unique SL structures and their biosynthetic enzymes in filamentous fungi make them an ideal drug target. Several studies have contributed towards the functional characterization of specific SL metabolism genes, which have been complemented by advanced lipidomics methods which allow accurate identification and quantification of lipid structures and pathway mapping. These studies have provided a better understanding of SL biosynthesis, degradation and regulation networks in filamentous fungi, which are discussed and elaborated here.