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Abstract Acute myeloid leukemia (AML) is fatal in the majority of adults. Identification of new therapeutic targets and their pharmacologic modulators are needed to improve outcomes. Previous studies had shown that immunization of rabbits with normal peripheral WBCs that had been incubated with fluorodinitrobenzene elicited high titer antibodies that bound to a spectrum of human leukemias. We report that proteomic analyses of immunoaffinity-purified lysates of primary AML cells showed enrichment of scaffolding protein IQGAP1. Immunohistochemistry and gene-expression analyses confirmed IQGAP1 mRNA overexpression in various cytogenetic subtypes of primary human AML compared to normal hematopoietic cells. shRNA knockdown of IQGAP1 blocked proliferation and clonogenicity of human leukemia cell-lines. To develop small molecules targeting IQGAP1 we performed in-silico screening of 212,966 compounds, selected 4 hits targeting the IQGAP1-GRD domain, and conducted SAR of the ‘fittest hit’ to identify UR778Br, a prototypical agent targeting IQGAP1. UR778Br inhibited proliferation, induced apoptosis, resulted in G2/M arrest, and inhibited colony formation by leukemia cell-lines and primary-AML while sparing normal marrow cells. UR778Br exhibited favorable ADME/T profiles and drug-likeness to treat AML. In summary, AML shows response to IQGAP1 inhibition, and UR778Br, identified through in-silico studies, selectively targeted AML cells while sparing normal marrow.

Abstract The principal cause of death in cancer patients is metastasis, which remains an unresolved problem. Conventionally, metastatic dissemination is linked to actomyosin‐driven cell locomotion. However, the locomotion of cancer cells often does not strictly line up with the measured actomyosin forces. Here, a complementary mechanism of metastatic locomotion powered by dynein‐generated forces is identified. These forces arise within a non‐stretchable microtubule network and drive persistent contact guidance of migrating cancer cells along the biomimetic collagen fibers. It is also shown that the dynein‐powered locomotion becomes indispensable during invasive 3D migration within a tissue‐like luminal network formed by spatially confining granular hydrogel scaffolds (GHS) made up of microscale hydrogel particles (microgels). These results indicate that the complementary motricity mediated by dynein is always necessary and, in certain instances, sufficient for disseminating metastatic breast cancer cells. These findings advance the fundamental understanding of cell locomotion mechanisms and expand the spectrum of clinical targets against metastasis.

Bacille Calmette-Guérin (BCG) vaccination supposedly imparts and augments “trained immunity” that cross-protects against multiple unrelated pathogens and enhances general immune surveillance. Gradual reductions in tuberculosis burden over the last 3–5 decades have resulted in the withdrawal of BCG vaccination mandates from developed industrialized countries while reducing to a single neonatal shot in the rest. Concurrently, a steady increase in early childhood Brain and CNS (BCNS) tumors has occurred. Though immunological causes of pediatric BCNS cancer are suspected, the identification of a causal protective variable with intervention potential has remained elusive. An examination of the countries with contrasting vaccination policies indicates significantly lower BCNS cancer incidence in 0–4-year-olds (per hundredthousand) of countries following neonatal BCG inoculations (n=146) vs. non-BCG countries (n=33) [Mean: 1.26 vs. 2.64; Median: 0.985 vs. 2.8; IQR: 0.31–2.0 vs. 2.4–3.2; P=

Preventive variables for childhood leukemia incidence (LI) remain unknown. Past assertions that childhood vaccinations, especially BCG, may be potentially protective have remained disputed for over five decades because of the lack of a unifying framework to explain variable outcomes in different studies. An examination of the early childhood LI for 2020 in European Region countries with supposedly similar underlying confounders but differential childhood vaccination coverage displays negative covariation with prevailing Mycobacterium spp. exposure in BCG-vaccinated children. The childhood LI in 0–4-year-old populations with >90% childhood BCG vaccination coverage is found to be strongly but negatively correlated with prevailing tuberculin immunoreactivity [r(24): -0.7868, p-value: < 0.0001]. No such correlation existed for the LI in 0–4-year-old populations without BCG vaccinations, though weak associations are hinted at by the available data for MCV2, PCV3, and DTP3 vaccinations. We hypothesize that early childhood BCG vaccination “priming” and subsequent “trained immunity” augmentation by “natural” boosting from Mycobacterium spp. exposure play a preventive and protective role in childhood LI. The non-consideration of prevailing “trained immunity” could have been a cause behind the conflicting outcomes in past studies. Exploratory studies, preferably performed in high-burden countries and controlling for the trained-immunity correlate and other potential confounders, would be warranted in order to establish a role for BCG vaccination and early-life immune training (or lack thereof) in childhood LI and help put the current controversy to rest.

Abstract Endeavors to identify potentially protective variables for COVID‐19 impact on certain populations have remained a priority. Multiple attempts have been made to attribute the reduced COVID‐19 impact on populations to their Bacillus–Calmette–Guérin (BCG) vaccination coverage ignoring the fact that the effect of childhood BCG vaccination wanes within 5 years while most of the COVID‐19 cases and deaths have occurred in aged with comorbidities. Since the supposed protection being investigated could come from heterologous ‘trained immunity’ (TI) conferred by exposure to Mycobacterium spp. (i.e., environmental and BCG), it is argued that the estimates of the prevalence of TI in populations currently available as latent tuberculosis infection (LTBI) prevalence would be a better variable to evaluate such assertions. Indeed, when we analyze the European populations (24), and erstwhile East and West Germany populations completely disregarding their BCG vaccination coverage, the populations with higher TI prevalence consistently display reduced COVID‐19 impact as compared to their lower TI prevalence neighbors. The TI estimates of the populations not the BCG coverage per se, negatively correlated with pandemic phase‐matched COVID‐19 incidences (r(24): −0.79 to −0.57; p‐value

Abstract Intensive breeding programs have increased rice yields, strongly contributing to increasing global food security during the post‐green revolution period. However, rice productivity has reached a yield barrier where further yield improvement is restricted by inadequate information on the association of yield components, and morphological and physiological traits with yield. We conducted a field experiment to evaluate (i) the contribution of morphological and physiological traits to yield and (ii) quantify the trade‐off effect between the yield components in rice, using a mini‐core collection of 362 rice genotypes comprising geographically distinct landraces and breeding lines. Our data point towards multiscale coordination of physiological and morphological traits associated with yield and biomass. Considerable trait variations across the genotypes in yield ranging from 0.5 to 78.5 g hill−1 and harvest index ranging from 0.7% to 60.7% highlight enormous diversity in rice across the globe. The natural elimination of trade‐off between yield components revealed the possibility to enhance rice yield in modern cultivars. Furthermore, our study demonstrated that genotypes with larger sink sizes could fix more carbon to achieve a higher yield. We propose that the knowledge thus generated in this study can be helpful for (a) trait‐based modeling and pyramiding alleles in rice‐breeding programs and (b) assisting breeders and physiologists in their efforts to improve crop productivity under a changing climate, thus harnessing the potential for sustainable productivity gains.

Therapy resistance is a significant concern while treating malignant disease. Accumulating evidence suggests that a subset of cancer cells potentiates tumor survival, therapy resistance, and relapse. Several different pathways regulate these purported cancer stem cells (CSCs). Evidence shows that the inflammatory tumor microenvironment plays a crucial role in maintaining the cancer stem cell pool. Typically, in the case of the tumor microenvironment, inflammatory pathways can be utilized by the tumor to aid in tumor progression; one such pathway is the CXCR1/2 pathway. The CXCR1 and CXCR2 receptors are intricately related, with CXCR1 binding two ligands that also bind CXCR2. They have the same downstream pathways but potentially separate roles in the tumor microenvironment. CXCR1 is becoming more well known for its role as a cancer stem cell identifier and therapeutic target. This review elucidates the role of the CXCR1 axis as a CSC marker in several solid tumors and discusses the utility of CXCR1 as a therapeutic target.

A pilot scale radiant wall oven (RWO) was used to bake potato strips at 12 different time-temperature combinations within 16 min at 290°C to 6.5 min at 365°C. Radiant and overall heat transfer coefficients were experimentally determined for each RWO treatment by monitoring temperature and heat flux. Correlation between heat transfer parameters and quality of the samples was also determined. It was determined that 92%–94% of the overall heat transfer coefficient was contributed by radiant heat transfer. While no correlation was found between color of the RWO baked potato strips and heat transfer coefficients, texture of the RWO baked potato strips was negatively correlated with overall and radiant heat transfer coefficients. Radiant heating could be used as a surface treatment to bake potato strips to mimic the surface of fried strips without increasing their fat content.

Fever remains an integral part of acute infectious diseases management, especially for those without effective therapeutics, but the widespread myths about “fevers” and the presence of confusing guidelines from different agencies, which have heightened during the coronavirus disease 2019 (COVID-19) pandemic and are open to alternate interpretation, could deny whole populations the benefits of fever. Guidelines suggesting antipyresis for 37.8–39°C fever are concerning as 39°C boosts the protective heat-shock and immune response (humoral, cell-mediated, and nutritional) whereas ≥40°C initiates/enhances the antiviral responses and restricts high-temperature adapted pathogens, e.g., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), strains of influenza, and measles. Urgent attention is accordingly needed to address the situation because of the potential public health consequences of the existence of conflicting guidelines in the public domain. We have in this article attempted to restate the benefits of fever in disease resolution, dispel myths, and underline the need for alignment of national treatment guidelines with that of the WHO, to promote appropriate practices and reduce the morbidity and mortality from infectious diseases, such as COVID-19.

Abstract Epithelial ovarian cancer (EOC) is a highly lethal gynecologic malignancy arising from the fallopian tubes that has a high rate of chemoresistant recurrence and low five-year survival rate. The ovarian cancer biomarker HE4 is known to promote proliferation, metastasis, chemoresistance, and suppression of cytotoxic lymphocytes. In this study, we sought to examine the effects of HE4 on signaling within diverse cell types that compose the tumor microenvironment. HE4 was found to activate STAT3 signaling and promote upregulation of the pro-angiogenic STAT3 target genes IL8 and HIF1A in immune cells, ovarian cancer cells, and endothelial cells. Moreover, HE4 promoted increases in tube formation in an in vitro model of angiogenesis, which was also dependent upon STAT3 signaling. Clinically, HE4 and IL8 levels positively correlated in ovarian cancer patient tissue. Furthermore, HE4 serum levels correlated with microvascular density in EOC tissue and inversely correlated with cytotoxic T cell infiltration, suggesting that HE4 may cause deregulated blood vessel formation and suppress proper T cell trafficking in tumors. Collectively, this study shows for the first time that HE4 has the ability to affect signaling events and gene expression in multiple cell types of the tumor microenvironment, which could contribute to angiogenesis and altered immunogenic responses in ovarian cancer.

Abstract Forchlorfenuron (FCF) is a synthetic plant cytokinin widely used in agriculture to promote fruit size, that paradoxically inhibits proliferation, migration, and invasion in human cancer cell lines. FCF has also been shown to affect HIF-1α and HER2, which are both known to play a crucial role in cancer cell survival. In this study, we have developed potent FCF analogs through structural modification of FCF, coined UR214-1, UR214-7, and UR214-9. Compared to parental FCF, these analogs are more effective in decreasing viability and proliferation in both ovarian and endometrial cancer cell lines. These FCF analogs also suppress HER2 expression at a concentration lower than that of FCF. In addition, we found that treatment with either FCF or its analogs decreases the expression of human epididymis protein 4 (HE4), which is commonly upregulated in ovarian and endometrial cancers. Given the association between cancer behavior and HE4 production in gynecologic cancers, our findings may provide insight useful in the development of new treatment strategies for gynecologic cancers.

Variation in methotrexate (MTX) efficacy represents a significant barrier to early and effective disease control in the treatment of autoimmune arthritis. We hypothesize that the utilization of metabolomic techniques will allow for an improved understanding of the biochemical basis for the pharmacological activity of MTX, and can promote the identification and evaluation of novel molecular biomarkers of MTX response. In this work, erythroblastoid cells were exposed to MTX at the physiologic concentration of 1,000 nM and analyzed using three metabolomic platforms to give a broad spectrum of cellular metabolites. MTX pharmacological activity, defined as cellular growth inhibition, was associated with an altered cellular metabolomic profile based on the analysis of 724 identified metabolites. By discriminant analysis, MTX treatment was associated with increases in ketoisovaleric acid, fructose, galactose, and 2‐deoxycytidine, and corresponding reductions in 2‐deoxyuridine, phosphatidylinositol 32:0, orotic acid, and inosine monophosphate. Inclusion of data from analysis of folate metabolism in combination with chemometric and metabolic network analysis demonstrated that MTX treatment is associated with dysregulated folate metabolism and nucleotide biosynthesis, which is in line with its known mechanism of action. However, MTX treatment was also associated with alterations in a diversity of metabolites, including intermediates of amino acid, carbohydrate, and lipid metabolism. Collectively, these findings support a robust metabolic response following exposure to physiologic concentrations of MTX. They also identify various metabolic intermediates that are associated with the pharmacological activity of MTX, and are, therefore, potential molecular biomarker candidates in future preclinical and clinical studies of MTX efficacy in autoimmune arthritis.

The changing consumer attitude toward meat products warrants innovation. Recent years have seen a continuous rise in the consumer demand for ready-to-eat meat products that trigger innovations in the manufacture of restructured meat products. This study was designed to develop meatloaf with the intention of using the downgraded stream of trimmed meat and meat by-products, which are known to contain a higher quantity of connecting tissue that causes tenderness issues, moisture retention, mouthfeel, and perceived food quality. The physicochemical effects of sodium bicarbonate, potassium bicarbonate, and salt alone or in combination on physicochemical and sensory characteristics of cooked ground beef were investigated. The results obtained showed that cooked ground beef without salt had the lowest cooked yield. Instrumental textural and sensory analysis revealed that bicarbonate-treated meatloaf samples exhibited significantly better sensory and textural properties than the control (p ≤0.05). Internal cooked color data revealed that meatloaf treated with sodium bicarbonate and potassium bicarbonate had a pinkish-red appearance with a significantly higher a∗ value (p ≤0.05). The findings provide evidence that inclusion of bicarbonates had a significant tenderizing and juiciness effects with improved sensory attributes of the meatloaf. The evidence presented clearly shows the potential of bicarbonate and salt will exert synergistic effects and improve eating quality and textural and sensorial attributes of meatloaf and other meat products.

The parasites of the genus Leishmania survive and proliferate in the host phagocytic cells by taking control over their microbicidal functions. The parasite also promotes differentiation of antigen-specific anti-inflammatory cytokines producing effector T cells, which eventually results in disease pathogenesis. The mechanisms that parasites employ to dominate host adaptive immunity are largely unknown. For the first time, we report that L. donovani, which causes visceral leishmaniasis in the Indian subcontinent, upregulates the expression of an immune inhibitory receptor i.e., CD300a on antigen presenting and phagocytic cells to dampen their effector functions. The blocking of CD300a signals in leishmania antigens activated macrophages and dendritic cells enhanced the production of nitric oxide, pro-inflammatory cytokines along with MHCI/II genes expression, and reduced parasitic uptake. Further, the abrogation of CD300a signals in Leishmania infected mice benefited antigen-experienced, i.e., CD4+CD44+ and CD8+CD44+ T cells to acquire more pro-inflammatory cytokines producing phenotypes and helped in the early clearance of parasites from their visceral organs. The CD300a receptor blocking also enhanced the conversion of CD4+ T effectors cells to their memory phenotypes i.e., CCR7high CD62Lhigh up to 1.6 and 1.9 fold after 14 and 21 days post-infection, respectively. These findings implicate that CD300a is an important determinant of host phagocytic cells functions and T cells differentiation against Leishmania antigens.

The impact of zinc (Zn) sufficiency/supplementation on COVID-19-associated mortality and incidence (SARS-CoV-2 infections) remains unknown. During an infection, the levels of free Zn are reduced as part of “nutritional immunity” to limit the growth and replication of pathogen and the ensuing inflammatory damage. Considering its key role in immune competency and frequently recorded deficiency in large sections of different populations, Zn has been prescribed for both prophylactic and therapeutic purposes in COVID-19 without any corroborating evidence for its protective role. Multiple trials are underway evaluating the effect of Zn supplementation on COVID-19 outcome in patients getting standard of care treatment. However, the trial designs presumably lack the power to identify negative effects of Zn supplementation, especially in the vulnerable groups of elderly and patients with comorbidities (contributing 9 out of 10 deaths; up to >8,000-fold higher mortality). In this study, we have analyzed COVID-19 mortality and incidence (case) data from 23 socially similar European populations with comparable confounders (population: 522.47 million; experiencing up to >150-fold difference in death rates) and at the matching stage of the pandemic (March 12 to June 26, 2020; first wave of COVID-19 incidence and mortality). Our results suggest a positive correlation between populations’ Zn-sufficiency status and COVID-19 mortality [r (23): 0.7893–0.6849, p-value < 0.0003] as well as incidence [r (23):0.8084–0.5658; p-value < 0.005]. The observed association is contrary to what would be expected if Zn sufficiency was protective in COVID-19. Thus, controlled trials or retrospective analyses of the adverse event patients’ data should be undertaken to correctly guide the practice of Zn supplementation in COVID-19.

Salinity stress is a major constraint to rice production in many coastal regions due to saline groundwater and river sources, especially during the dry season in coastal areas when seawater intrudes further inland due to reduced river flows. Since salinity tolerance is a complex trait, breeding efforts can be assisted by mapping quantitative trait loci (QTLs) for complementary salt tolerance mechanisms, which can then be combined to provide higher levels of tolerance. While an abundance of seedling stage salinity tolerance QTLs have been mapped, few studies have investigated reproductive stage tolerance in rice due to the difficulty of achieving reliable stage-specific phenotyping techniques. In the current study, a BC1F2 mapping population consisting of 435 individuals derived from a cross between a salt-tolerant Saudi Arabian variety, Hasawi, and a salt-sensitive Bangladeshi variety, BRRI dhan28, was evaluated for yield components after exposure to EC 10 dS/m salinity stress during the reproductive stage. After selecting tolerant and sensitive progeny, 190 individuals were genotyped by skim sequencing, resulting in 6209 high quality single nucleotide polymorphic (SNP) markers. Subsequently, a total of 40 QTLs were identified, of which 24 were for key traits, including productive tillers, number and percent filled spikelets, and grain yield under stress. Importantly, three yield-related QTLs, one each for productive tillers (qPT3.1), number of filled spikelets (qNFS3.1) and grain yield (qGY3.1) under salinity stress, were mapped at the same position (6.7 Mb or 26.1 cM) on chromosome 3, which had not previously been associated with grain yield under salinity stress. These QTLs can be investigated further to dissect the molecular mechanisms underlying reproductive stage salinity tolerance in rice.

Advanced clear cell ovarian cancer (CCOC) is a highly fatal malignancy with a scarcity of effective treatment options. CCOC is inherently chemotherapy resistance, but the exact mechanism of this resistance has yet to be established. Prosurvival signaling, such as through the MAPK cascade, is one way in which cancer cells can evade chemotherapy. We have determined that CCOC exhibits baseline elevated levels of MAPK activity, which increase further upon cisplatin exposure. We have developed a novel MEK inhibitor, URML-3881, to test the effect of MAPK inhibition in CCOC. URML-3881 was found to reduce in vitro CCOC viability through apoptosis and proliferation inhibition, yet it failed to induce in vivo tumor regression. Similarly, cisplatin alone had minimal impact on tumor growth, but remarkably, the combination of MEK inhibition and cisplatin led to a significant and prolonged tumor regression. These studies confirm that the combination of MEK inhibition with URML-3881 and cisplatin is superior to either agent alone in CCOC. Our data support the design of future preclinical and clinical studies into the combination of MEK inhibition and platinum-based chemotherapy as a treatment strategy for CCOC.

Chicken breast meat is traditionally marinated to improve tenderness and juiciness. However, a significant amount of marinade is purged during cooking. It was envisioned that preheating of marinated chicken breast meat would minimize the purge due to presetting the myofibrillar proteins and will give higher cook yield. The preheating was done in a radiofrequency (RF) oven to provide uniform heating within the volume of the product, and to allow extra marinade retention. Two preheating regimens, 20–30°C and 55–60°C were selected. A 3–4% marinade gain was obtained while the meat was preheated in RF with 10% extra marinade but this gain was not significantly different in the four treatments and the control (p > .05). The cooked meat yields were determined as a function of programmed preheating of marinated meat in the RF oven, followed by final cooking of the product in the air impingement oven. The programmed preheated samples at 20–30°C showed higher cook yield (96.11–100.51%) as compared to the control (95.6%). However, all the samples heated at 55–60°C showed higher cook yield (100.57–109.39%). Warner-Bratzler shear tests were performed on cooked samples to determine the quality of RF preheated product, and the quality of the RF-treated product was not much different from that of the product cooked directly in a conventional air oven.

Arctic coasts, which feature land-ocean transport of freshwater, sediments, and other terrestrial material, are impacted by climate change, including increased temperatures, melting glaciers, changes in precipitation and runoff. These trends are assumed to affect productivity in fjordic estuaries. However, the spatial extent and temporal variation of the freshwater-driven darkening of fjords remain unresolved. The present study illustrates the spatio-temporal variability of suspended particulate matter (SPM) in the Adventfjorden estuary, Svalbard, using in-situ field campaigns and ocean colour remote sensing (OCRS) via high-resolution Sentinel-2 imagery. To compute SPM concentration (CSPMsat), a semi-analytical algorithm was regionally calibrated using local in-situ data, which improved the accuracy of satellite-derived SPM concentration by ~20% (MRD). Analysis of SPM concentration for two consecutive years (2019, 2020) revealed strong seasonality of SPM in Adventfjorden. Highest estimated SPM concentrations and river plume extent (% of fjord with CSPMsat > 30 mg L−1) occurred during June, July, and August. Concurrently, we observed a strong relationship between river plume extent and average air temperature over the 24 h prior to the observation (R2 = 0.69). Considering predicted changes to environmental conditions in the Arctic region, this study highlights the importance of the rapidly changing environmental parameters and the significance of remote sensing in analysing fluxes in light attenuating particles, especially in the coastal Arctic Ocean.

Abstract Background Pancreatic cancer (PC) is a highly aggressive disease, and the lethality of this disease stems from early metastatic dissemination where surgical removal cannot provide a cure. Improvement of the therapeutic outcome and overall survival of PC patients requires to understand the fundamental processes that lead to metastasis such as the gain of cellular migration ability. One such family of proteins, which are essential players of cellular migration, is Semaphorin. Previously, we have identified one of the Semaphorin family member, Semaphorin-5A (SEMA5A) to be involved in organ-specific homing during PC metastasis. We have also demonstrated that SEMA5A has a constitutive expression in PC cell lines derived from metastatic sites in comparison with low endogenous expression in the primary tumor-derived cell line. In this study, we examined whether constitutive SEMA5A expression in metastatic PC cells regulates tumor growth and metastatic potential. Methods We generated SEMA5A knockdown in T3M-4 and CD18/HPAF cells and assessed their phenotypes on in vitro motility, tumor growth, and metastatic progression. Results In contrary to our initial expectations, orthotopic injection of SEMA5A knockdown cells into nude mice resulted in a significant increase in both tumor burden and liver metastases in comparison with the Control cells. Similarly, we observed higher in vitro migratory potential with pronounced morphological changes associated with epithelial-mesenchymal transition (EMT), a decrease in the expression of epithelial marker E-cadherin (E-Cad), increase in the expression of mesenchymal markers N-cadherin (N-Cad) and Snail and the activation of the Wnt-signaling pathway in SEMA5A knockdown cells. Furthermore, re-establishing SEMA5A expression with a knockdown resistant mouse Sema5A in SEMA5A knockdown cells resulted in a reversion to the epithelial state (mesenchymal-epithelial transition; MET), as indicated by the rescue of E-Cad expression and a decrease in N-Cad and Snail expression. Conclusions Collectively, our data suggest that SEMA5A expression maintains epithelial phenotype in the metastatic microenvironment.

While high-load resistance training increases muscle hypertrophy, the intramuscular protein responses to this form of training remains largely unknown. In the current study, recreationally resistance-trained college-aged males (N = 15; mean ± SD: 23 ± 3 years old, 6 ± 5 years training) performed full-body, low-volume, high-load [68–90% of one repetition maximum (1RM)] resistance training over 10 weeks. Back squat strength testing, body composition testing, and a vastus lateralis biopsy were performed before (PRE) and 72 h after the 10-week training program (POST). Fiber type-specific cross-sectional area (fCSA), myofibrillar protein concentrations, sarcoplasmic protein concentrations, myosin heavy chain and actin protein abundances, and muscle tissue percent fluid were analyzed. The abundances of individual sarcoplasmic proteins in 10 of the 15 participants were also assessed using proteomics. Significant increases (p < 0.05) in type II fCSA and back squat strength occurred with training, although whole-body fat-free mass paradoxically decreased (p = 0.026). No changes in sarcoplasmic protein concentrations or muscle tissue percent fluid were observed. Myosin heavy chain protein abundance trended downward (−2.9 ± 5.8%, p = 0.069) and actin protein abundance decreased (−3.2 ± 5.3%, p = 0.034) with training. Proteomics indicated only 13 sarcoplasmic proteins were altered with training (12 up-regulated, 1 down-regulated, p < 0.05). Bioinformatics indicated no signaling pathways were affected, and proteins involved with metabolism (e.g., ATP-PCr, glycolysis, TCA cycle, or beta-oxidation) were not affected. These data comprehensively describe intramuscular protein adaptations that occur following 10 weeks of high-load resistance training. Although previous data from our laboratory suggests high-volume resistance training enhances the ATP-PCr and glycolytic pathways, we observed different changes in metabolism-related proteins in the current study with high-load training.

With the ever-increasing world population, an extra 1.5 billion mouths need to be fed by 2050 with continuously dwindling arable land. Hence, it is imperative that extra food come from the marginal lands that are expected to be unsuitable for growing major staple crops under the adverse climate change scenario. Crop diversity provides right alternatives for marginal environments to improve food, feed, and nutritional security. Well-adapted and climate-resilient crops will be the best fit for such a scenario to produce seed and biomass. The minor millets are known for their high nutritional profile and better resilience for several abiotic stresses that make them the suitable crops for arid and salt-affected soils and poor-quality waters. Finger millet (Eleucine coracana) and foxtail millet (Setaria italica), also considered as orphan crops, are highly tolerant grass crop species that grow well in marginal and degraded lands of Africa and Asia with better nutritional profile. Another category of grains, called pseudo-cereals, is considered as rich foods because of their protein quality and content, high mineral content, and healthy and balance food quality. Quinoa (Chenopodium quinoa), amaranth (Amaranthus sp.), and buckwheat (Fagopyrum esculentum) fall under this category. Nevertheless, both minor millets and pseudo-cereals are morphologically different, although similar for micronutrient bioavailability, and their grains are gluten-free. The cultivation of these millets can make dry lands productive and ensure future food as well as nutritional security. Although the natural nutrient profile of these crop plant species is remarkably good, little development has occurred in advances in molecular genetics and breeding efforts to improve the bioavailability of nutrients. Recent advances in NGS have enabled the genome and transcriptome sequencing of these millets and pseudo-cereals for the faster development of molecular markers and application in molecular breeding. Genomic information on finger millet (1,196 Mb with 85,243 genes); S. italica, a model small millet (well-annotated draft genome of 420 Mb with 38,801 protein-coding genes); amaranth (466 Mb genome and 23,059 protein-coding genes); buckwheat (genome size of 1.12 Gb with 35,816 annotated genes); and quinoa (genome size of 1.5 Gb containing 54,438 protein-coding genes) could pave the way for the genetic improvement of these grains. These genomic resources are an important first step toward genetic improvement of these crops. This review highlights the current advances and available resources on genomics to improve nutrient bioavailability in these five suitable crops for the sustained healthy livelihood.

RNA interference (RNAi) molecules have tremendous potential for cancer therapy but are limited by insufficient potency after intravenous (IV) administration. We previously found that polymer complexes (polyplexes) formed between 3′-cholesterol-modified siRNA (Chol-siRNA) or DsiRNA (Chol-DsiRNA) and the cationic diblock copolymer PLL[30]-PEG[5K] greatly increase RNAi potency against stably expressed LUC mRNA in primary syngeneic murine breast tumors after daily IV dosing. Chol-DsiRNA polyplexes, however, maintain LUC mRNA suppression for ~48 h longer after the final dose than Chol-siRNA polyplexes, which suggests that they are the better candidate formulation. Here, we directly compared the activities of Chol-siRNA polyplexes and Chol-DsiRNA polyplexes in primary murine 4T1 breast tumors against STAT3, a therapeutically relevant target gene that is overexpressed in many solid tumors, including breast cancer. We found that Chol-siSTAT3 polyplexes suppressed STAT3 mRNA in 4T1 tumors with similar potency (half-maximal ED50 0.3 mg/kg) and kinetics (over 96 h) as Chol-DsiSTAT3 polyplexes, but with slightly lower activity against total Stat3 protein (29% vs. 42% suppression) and tumor growth (11.5% vs. 8.6% rate-based T/C ratio) after repeated IV administration of equimolar, tumor-saturating doses every other day. Thus, both Chol-siRNA polyplexes and Chol-DsiRNA polyplexes may be suitable clinical candidates for the RNAi therapy of breast cancer and other solid tumors.

The present study was aimed to identify the underlying mechanisms of improper renal function in Leishmania donovani infection that causes VL. Mice (BALB/c) were infected with L. donovani and different parameters for proteinuria were assessed. The levels of superoxide anion (O2−), hydrogen peroxide (H2O2), lipid peroxidation (MDA), inflammatory cytokines, and toll-like receptor (TLR) 2 and 4 expression were found significantly elevated at 60th day in these animals and declined at 90th day post infection. However, TGF-β and caspase 3 activities were higher at 90th day in comparison to 60th day post infection. These findings suggested that exacerbated inflammatory conditions correlate with abnormal renal functions in L. donovani infection, which is further augmented by activated TLRs expressions by circulating leishmanial antigens. Further, the increased levels of TGF-β and caspase 3 at 90th day suggested TGF-β mediated apoptotic cell death of renal and other cells during later stages of disease that may eventually result in release of host and parasitic factors in urine during visceral leishmaniasis. Keywords: Leishmaniasis, Renal, TLRs, Apoptosis

Applied physics: New technique for oxide interfaces Recent advances in synthesizing and engineering oxide interfaces and heterostructures have provided a powerful strategy for creating new artificial structures exhibiting phenomena not possible in other materials form. Now Professor Xiaoxing Xi at Temple University from the US collaborates with researchers from the US, Italy and China showing a success in constructing oxides with well controlled stoichiometry and atomic layer precision. The central method—atomic layer-by-layer laser molecular beam epitaxy (ALL-Laser MBE)—is built upon the combined strengths of molecular beam epitaxy and pulsed laser deposition. It allows not only the growth of thin films of a Ruddlesden-Popper phase La5Ni4O13, but LaAlO3/SrTiO3 interfaces. Remarkably, no oxygen vacancies are detected in the oxide interfaces because of the high oxygen pressures during the growth and the carrier density of the two-dimensional electron gas agrees with the electronic reconstruction mechanism.

While selective overexpression of serum clinical biomarker Human epididymis secretory protein 4 (HE4) is indicative of ovarian cancer tumorigenesis, much is still known about the mechanistic role of the HE4 gene or gene product. Here, we examine the role of the secretory glycoprotein HE4 in ovarian cancer immune evasion. Through modified subtractive hybridization analyses of human peripheral blood mononuclear cells (PBMCs), we have characterized gene targets of HE4 and established a preliminary mechanism of HE4-mediated immune failure in ovarian tumors. Dual specificity phosphatase 6 (DUSP6) emerged as the most upregulated gene in PBMCs upon in vitro exposure to HE4. DUSP6 was found to be upregulated in CD8+ cells and CD56+ cells. HE4 exposure reduced Erk1/2 phosphorylation specifically in these cell populations and the effect was erased by co-incubation with a DUSP6 inhibitor, (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI). In co-culture with PBMCs, HE4-silenced SKOV3 human ovarian cancer cells exhibited enhanced proliferation upon exposure to external HE4, while this effect was partially attenuated by adding BCI to the culture. Additionally, the reversal effects of BCI were erased in the co-culture with CD8+ / CD56+ cell deprived PBMCs. Taken together, these findings show that HE4 enhances tumorigenesis of ovarian cancer by compromising cytotoxic CD8+ and CD56+ cells through upregulation of self-produced DUSP6.

Resistance training generally increases skeletal muscle hypertrophy, whereas aging is associated with a loss in muscle mass. Interestingly, select studies suggest that aging, as well as resistance training, may lead to a reduction in the abundance of skeletal muscle myofibrillar (or contractile) protein (per mg tissue). Proteomic interrogations have also demonstrated that aging, as well as weeks to months of resistance training, lead to appreciable alterations in the muscle proteome. Given this evidence, the purpose of this small pilot study was to examine total myofibrillar as well as total sarcoplasmic protein concentrations (per mg wet muscle) from the vastus lateralis muscle of males who were younger and resistance-trained (denoted as YT, n = 6, 25 ± 4 years old, 10 ± 3 self-reported years of training), younger and untrained (denoted as YU, n = 6, 21 ± 1 years old), and older and untrained (denoted as OU, n = 6, 62 ± 8 years old). The relative abundances of actin and myosin heavy chain (per mg tissue) were also examined using SDS-PAGE and Coomassie staining, and shotgun proteomics was used to interrogate the abundances of individual sarcoplasmic and myofibrillar proteins between cohorts. Whole-body fat-free mass (YT > YU = OU), VL thickness (YT > YU = OU), and leg extensor peak torque (YT > YU = OU) differed between groups (p < 0.05). Total myofibrillar protein concentrations were greater in YT versus OU (p = 0.005), but were not different between YT versus YU (p = 0.325). The abundances of actin and myosin heavy chain were greater in YT versus YU (p < 0.05) and OU (p < 0.001). Total sarcoplasmic protein concentrations were not different between groups. While proteomics indicated that marginal differences existed for individual myofibrillar and sarcoplasmic proteins between YT versus other groups, age-related differences were more prominent for myofibrillar proteins (YT = YU > OU, p < 0.05: 7 proteins; OU > YT = YU, p < 0.05: 11 proteins) and sarcoplasmic proteins (YT = YU > OU, p < 0.05: 8 proteins; OU > YT&YU, p < 0.05: 29 proteins). In summary, our data suggest that modest (~9%) myofibrillar protein packing (on a per mg muscle basis) was evident in the YT group. This study also provides further evidence to suggest that notable skeletal muscle proteome differences exist between younger and older humans. However, given that our n-sizes are low, these results only provide a preliminary phenotyping of the reported protein and proteomic variables.

Oxidative stress and neuroinflammation play a key role in dopaminergic (DA) neuronal degeneration, which results in the hindrance of normal ongoing biological processes in the case of Parkinson’s disease. As shown in several studies, on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration, different behavioral parameters have suggested motor impairment and damage of antioxidant defence. Thus, some specific biological molecules found in medicinal plants can be used to inhibit the DA neuronal degeneration through their antioxidant and anti-inflammatory activities. With this objective, we studied chlorogenic acid (CGA), a naturally occurring polyphenolic compound, for its antioxidant and anti-inflammatory properties in MPTP-intoxicated mice. We observed significant reoccurrence of motor coordination and antioxidant defence on CGA supplementation, which has been in contrast with MPTP-injected mice. Moreover, in the case of CGA-treated mice, the enhanced expression of tyrosine hydroxylase (TH) within the nigrostriatal region has supported its beneficial effect. The activation of glial cells and oxidative stress levels were also estimated using inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP) immunoreactivity within substantia nigra (SN) and striatum of MPTP-injected mice. Administration of CGA has prevented the neuroinflammation in SN by regulating the nuclear factor-κB expression in the MPTP-induced group. The significant release of certain pro-inflammatory mediators such as tumor necrosis factor-α and interleukin (IL)-1β has also been inhibited by CGA with the enhanced expression of anti-inflammatory cytokine IL-10. Moreover, reduced GFAP staining within the nigrostriatal region has supported the fact that CGA has significantly helped in the attenuation of astrocyte activation. Hence, our study has shown that CGA supplementation shows its therapeutic ability by reducing the oxidative stress and neuroinflammation in MPTP-intoxicated mice.

The protozoan parasite Leishmania has evolved several strategies to undermine host defense mechanisms by inducing Th2-type adaptive immunity and suppressing effector functions of Th1 phenotype. In our earlier studies, using centrin gene-deleted Leishmania (LdCen−/−) parasites as an immunogen, we have shown induction of an effective Th1-type immunity and robust memory responses that mediate protection against virulent challenge. However, role of inhibitory signals in Leishmania vaccine induced immunity in general, and LdCen−/− in particular has not been studied. Herein, we report that immunization with LdCen−/− parasites produces more functional Th1-type CD4+ T cells via downregulation of CD200–CD200R immune inhibitory axis compared to wild-type infection. We found that expression of CD200 and CD200R was significantly reduced in LdCen−/− infection compared to wild-type infection. Diminished CD200–CD200R signaling in LdCen−/− infection enabled proliferation of CD4+ T cells and resulted in the induction of pro-inflammatory cytokines and suppression of anti-inflammatory response. The effects of diminished CD200–CD200R signaling by LdCen−/− were most evident in the suppression of IL-10-producing CD4+ T cells that helped enhance more Th1 cytokine producing and multi-functional T cells compared to wild-type infection. In vivo blocking of CD200 expression with anti-CD200 treatment in wild-type infected mice limited Th2 response as indicated by reduction of IL-10-producing Tr1 cells and reduced parasite burden. On the other hand, treatment with anti-CD200 improved the LdCen−/− vaccine-induced multifunctional response and reduction in splenic parasite load upon challenge. Taken together, these studies demonstrate the role of CD200–CD200R signals in the protection induced by LdCen−/− parasites.

Micro RNAs (miRNAs) have emerged as a critical regulator of several biological processes in both animals and plants. They have also been associated with regulation of immune responses in many human diseases during recent years. Visceral leishmaniasis (VL) is the most severe form of leishmaniasis, which is characterized by impairment of both innate and adaptive immune responses. In the present study, we observed that Leishmania establishes hypoxic environment in host macrophages that induces the expression of hypoxia inducible factor-1α (HIF-1α) and miRNA-210. Further, the expression of miRNA-210 was found to be dependent on activation of HIF-1α expression. The HIF-1α silencing by siRNA resulted in significantly (p < 0.001) decreased expression of miR-210 in parasites infected macrophages. We also observed that in siHIF-1α or antagomir-210 treated L. donovani infected macrophages, the parasitic load and percentage infectivity were significantly (p < 0.001) decreased. Furthermore, we found that inhibition of miR-210 leads to activation of NF-κB subunit p50, and it forms heterodimer with p65 and translocates into the nucleus from the cytoplasm. This significantly (p < 0.05) induced the transcription of pro-inflammatory cytokines genes such as TNF-α and IL-12 in miRNA-210 inhibited macrophages compared to uninhibited macrophages whereas the level of IL-10, an anti-inflammatory cytokine, was found to be significantly decreased (p < 0.001). These findings suggested that L. donovani infection induces hypoxic environment inside the macrophages that activates HIF-1α. Further, HIF-1α upregulates miR-210, which eventually establishes a suitable environment for the survival of parasite inside the host macrophages by downregulating NF-κB mediated pro-inflammatory immune responses.

The main objective of this study was to determine the effectiveness of infrared technology for blanching small-sized peanuts. A radiant wall oven was used for infrared blanching. Infrared treatments included 343°C for 60 s and 288°C for 90 s. High and low moisture groups with approximate moisture content of 9% and 6% were used. An impingement oven set at 100°C for 20 min was used as the control treatment. No treatment differed from control in terms of blanchability. A descriptive sensory shelf life study of six weeks found no evidence of oxidative changes in experimental treatments. The infrared blanched peanuts were roasted using an impingement oven set to 177°C for 10 min for a consumer acceptability test. Conventionally blanched peanuts roasted under the same parameters were used as a control. The consumer panel found the peanuts blanched by infrared radiation at 343°C for 60 s to be the most likeable roasted IR sample and did not differ from control. IR heating is a viable and quicker alternative to blanch small-sized peanut varieties with minimal effects on quality including sensory properties.

Chronic exposure to high levels of inorganic arsenic (iAs) has been associated with cancerous and non-cancerous health effects, including cardiovascular effects. However, the mechanism for a presumed toxic effect of arsenic on vascular tissue is not clear. Our working hypothesis is that inorganic trivalent arsenic and its methylated metabolites react with cysteine-containing cellular proteins and alter their function leading to adverse events such as cytotoxicity or proliferation. In this study, human microvascular endothelial cells (HMEC1) and mouse microvascular endothelial cells (MFP-MVEC) were exposed to arsenite (iAsIII), monomethylarsonous acid (MMAIII), or dimethylarsinous acid (DMAIII) for 72 h to evaluate cytotoxicity, and for 24, 48 or 72 h to evaluate cell proliferation. Both cell lines showed similar LC50 values, from 0.1 to 2.4 μM, for all three trivalent arsenicals. The endothelial cells treated with1 nM to 1 μM concentrations of the three trivalent arsenicals did not show increased cell proliferation at 24, 48 or 72 h or increased rate of proliferation at 72 h of exposure. Overall, cytotoxicity of trivalent arsenicals to microvascular endothelial cells is similar to their cytotoxicity to epithelial cells, and that these compounds are not mitogenic.

Neuropilins (NRPs) are non-tyrosine kinase cell surface glycoproteins expressed in all vertebrates and widely conserved across species. The two isoforms, such as neuropilin-1 (NRP1) and neuropilin-2 (NRP2), mainly act as coreceptors for class III Semaphorins and for members of the vascular endothelial growth factor family of molecules and are widely known for their role in a wide array of physiological processes, such as cardiovascular, neuronal development and patterning, angiogenesis, lymphangiogenesis, as well as various clinical disorders. Intriguingly, additional roles for NRPs occur with myeloid and lymphoid cells, in normal physiological as well as different pathological conditions, including cancer, immunological disorders, and bone diseases. However, little is known concerning the molecular pathways that govern these functions. In addition, NRP1 expression has been characterized in different immune cellular phenotypes including macrophages, dendritic cells, and T cell subsets, especially regulatory T cell populations. By contrast, the functions of NRP2 in immune cells are less well known. In this review, we briefly summarize the genomic organization, structure, and binding partners of the NRPs and extensively discuss the recent advances in their role and function in different immune cell subsets and their clinical implications.

Bacterial biofilm has been reported to be associated with more than 80% of bacterial infections. Curcumin, a hydrophobic polyphenol compound, has anti-quorum sensing activity apart from having antimicrobial action. However, its use is limited by its poor aqueous solubility and rapid degradation. In this study, we attempted to prepare quantum dots of the drug curcumin in order to achieve enhanced solubility and stability and investigated for its antimicrobial and antibiofilm activity. We utilized a newer two-step bottom up wet milling approach to prepare Curcumin Quantum Dots (CurQDs) using acetone as a primary solvent. Minimum inhibitory concentration against select Gram-positive and Gram-negative bacteria was performed. The antibiofilm assay was performed at first using 96-well tissue culture plate and subsequently validated by Confocal Laser Scanning Microscopy. Further, biofilm matrix protein was isolated using formaldehyde sludge and TCA/Acetone precipitation method. Protein extracted was incubated with varying concentration of CurQDs for 4 h and was subjected to SDS–PAGE. Molecular docking study was performed to observe interaction between curcumin and phenol soluble modulins as well as curli proteins. The biophysical evidences obtained from TEM, SEM, UV-VIS, fluorescence, Raman spectroscopy, and zeta potential analysis confirmed the formation of curcumin quantum dots with increased stability and solubility. The MICs of curcumin quantum dots, as observed against both select gram positive and negative bacterial isolates, was observed to be significantly lower than native curcumin particles. On TCP assay, Curcumin observed to be having antibiofilm as well as biofilm degrading activity. Results of SDS–PAGE and molecular docking have shown interaction between biofilm matrix proteins and curcumin. The results indicate that aqueous solubility and stability of Curcumin can be achieved by preparing its quantum dots. The study also demonstrates that by sizing down the particle size has not only enhanced its antimicrobial properties but it has also shown its antibiofilm activities. Further, study is needed to elucidate the exact nature of interaction between curcumin and biofilm matrix proteins.

The outcome of Leishmania infection depends on parasite abilities to evade host immune response and its survival in hostile environment of host macrophages. Despite a wealth of gained crucial information, parasite strategies by which it dampens host macrophage functions remain poorly understood. Micro RNAs (miRNAs) are evolutionarily conserved class of endogenous 22-nucleotide small non-coding RNA gene products, described to participate in the regulation of almost every cellular process investigated so far. In this study, we identified 940 miRNAs in Leishmania donovani infected macrophages by de novo sequencing out of which levels of 85 miRNAs were found to be consistently modified by parasite infection. Herein, we report the functional characteristics of 10 miRNAs i.e., mir-3620, mir-6385, mir-6973a, mir-6996, mir-328, mir-8113, mir-3473f, mir-763, mir-6540, and mir-1264 that were differentially but constantly regulated in infected macrophages for their role in regulation of macrophage effector functions. The target gene prediction and biological interaction analysis revealed involvement of these miRNAs in various biological processes such as apoptosis inhibition, phagocytosis, drug response, and T cell phenotypic transitions. These findings could contribute for the better understanding of macrophages dysfunction and leishmanial pathogenesis. Further, the identified miRNAs could also be used as biomarker/s in diagnosis, prognosis, and therapeutics of Leishmania infection.

Most breast cancer patients die due to bone metastasis. Although metastasis accounts for 5% of the breast cancer cases, it is responsible for most of the deaths. Sometimes even before the detection of a primary tumor, most of the patients have bone and lymph node metastasis. Moreover, at the time of death, breast cancer patients have the bulk of the tumor burden in their bones. Therapy options are available for the treatment of primary tumors, but there are minimal options for treating breast cancer patients who have bone metastasis. C-X-C motif chemokine receptor type 2 (CXCR2) receptor-mediated signaling has been shown to play a critical role during bone-related inflammations and its ligands C-X-C motif chemokine ligand 6 (CXCL6) and 8 (CXCL8) aid in the resorption of bone during bone metastasis. In this study, we tested the hypothesis that CXCR2 contributes to mammary tumor-induced osteolysis and bone metastasis. In the present study, we examined the role of both tumor cell-derived and host-derived CXCR2 in influencing mammary tumor cell bone metastasis. For understanding the role of tumor cell-derived CXCR2, we utilized Cl66 CXCR2 knockdown (Cl66-shCXCR2) and Cl66-Control cells (Cl66-Control) and observed a significant decrease in tumor growth and tumor-induced osteolysis in Cl66-shCXCR2 cells in comparison with the Cl66-Control cells. Next, for understanding the role of host-derived CXCR2, we utilized mice with genomic knockdown of CXCR2 (Cxcr2−/−) and injected Cl66-Luciferase (Cl66-Luc) or 4T1-Luciferase (4T1-Luc) cells. We observed decreased bone destruction and metastasis in the bone of Cxcr2−/− mice. Our data suggest the importance of both tumor cell- and host-derived CXCR2 signaling in the bone metastasis of breast cancer cells.

In the post-genomic era, computational identification of cell adhesion molecules (CAMs) becomes important in defining new targets for diagnosis and treatment of various diseases including cancer. Lack of a comprehensive CAM-specific database restricts our ability to identify and characterize novel CAMs. Therefore, we developed a comprehensive mammalian cell adhesion molecule (MCAM) database. The current version is an interactive Web-based database, which provides the resources needed to search mouse, human and rat-specific CAMs and their sequence information and characteristics such as gene functions and virtual gene expression patterns in normal and tumor tissues as well as cell lines. Moreover, the MCAM database can be used for various bioinformatics and biological analyses including identifying CAMs involved in cell-cell interactions and homing of lymphocytes, hematopoietic stem cells and malignant cells to specific organs using data from high-throughput experiments. Furthermore, the database can also be used for training and testing existing transmembrane (TM) topology prediction methods specifically for CAM sequences. The database is freely available online at http://app1.unmc.edu/mcam.

A novel flavonoid C-glycoside, 5-hydroxy-7-methoxy-6-C-glycosylflavone (1), was isolated from the aerial part of Sphaeranthus indicus. Its structure was elucidated by spectroscopic methods.

The present work analyzed soy milk prepared from whole dehulled soybeans. The traditional method of soy milk preparation leads to wastage of about 35% of soybean solids in the form of okara, which gets filtered out. In the current study, soy milk was prepared with practically 100% recovery of soybean solids and treated with continuous flow high pressure processing (207 and 276 MPa pressure, 121 and 145 °C exit temperatures, and 0.75 and 1.25 L/min flow rates), and the changes in the physical, chemical, microbial, and sensory properties during 28 days of storage at 4 °C were analyzed. The treated soy milk remained stable for 28 days. There was a significant reduction in the particle size of soybean solids which did not change during storage. The pH of the treated soy milk was significantly lower than the untreated soy milk and it reduced further upon storage. The soy milk was pasteurized with high pressure processing coupled with preheating. No lipoxygenase activity was detected. Compared to commercial samples, there was no significant difference in the astringency, bitterness, or chalkiness of soy milk prepared in the study.

In the post-genomic era, computational identification of cell adhesion molecules (CAMs) becomes important in defining new targets for diagnosis and treatment of various diseases including cancer. Lack of a comprehensive CAM-specific database restricts our ability to identify and characterize novel CAMs. Therefore, we developed a comprehensive mammalian cell adhesion molecule (MCAM) database. The current version is an interactive Web-based database, which provides the resources needed to search mouse, human and rat-specific CAMs and their sequence information and characteristics such as gene functions and virtual gene expression patterns in normal and tumor tissues as well as cell lines. Moreover, the MCAM database can be used for various bioinformatics and biological analyses including identifying CAMs involved in cell-cell interactions and homing of lymphocytes, hematopoietic stem cells and malignant cells to specific organs using data from high-throughput experiments. Furthermore, the database can also be used for training and testing existing transmembrane (TM) topology prediction methods specifically for CAM sequences. The database is freely available online at http://www.app1.unmc.edu/mcam .