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Goldberg, D. ; Charni-Natan, M. ; Buchshtab, N. ; Bar-Shimon, M. ; Goldstein, I. Hormone-controlled cooperative binding of transcription factors drives synergistic induction of fasting-regulated genes. Nucleic Acids Res 2022, gkac358. Publisher's VersionAbstract
During fasting, hepatocytes produce glucose in response to hormonal signals. Glucagon and glucocorticoids are principal fasting hormones that cooperate in regulating glucose production via gluconeogenesis. However, how these hormone signals are integrated and interpreted to a biological output is unknown. Here, we use genome-wide profiling of gene expression, enhancer dynamics and transcription factor (TF) binding in primary mouse hepatocytes to uncover the mode of cooperation between glucagon and glucocorticoids. We found that compared to a single treatment with each hormone, a dual treatment directs hepatocytes to a pro-gluconeogenic gene program by synergistically inducing gluconeogenic genes. The cooperative mechanism driving synergistic gene expression is based on ‘assisted loading’ whereby a glucagon-activated TF (cAMP responsive element binding protein; CREB) leads to enhancer activation which facilitates binding of the glucocorticoid receptor (GR) upon glucocorticoid stimulation. Glucagon does not only activate single enhancers but also activates enhancer clusters, thereby assisting the loading of GR also across enhancer units within the cluster. In summary, we show that cells integrate extracellular signals by an enhancer-specific mechanism: one hormone-activated TF activates enhancers, thereby assisting the loading of a TF stimulated by a second hormone, leading to synergistic gene induction and a tailored transcriptional response to fasting.
Gonzalez, A. ; Cheung, W. W. ; Perens, E. A. ; Oliveira, E. A. ; Gertler, A. ; Mak, R. H. A Leptin Receptor Antagonist Attenuates Adipose Tissue Browning and Muscle Wasting in Infantile Nephropathic Cystinosis-Associated Cachexia. CELLS 2021, 10.Abstract
Mice lacking the functional cystinosin gene (Ctns(-/-)), a model of infantile nephropathic cystinosis (INC), exhibit the cachexia phenotype with adipose tissue browning and muscle wasting. Elevated leptin signaling is an important cause of chronic kidney disease-associated cachexia. The pegylated leptin receptor antagonist (PLA) binds to but does not activate the leptin receptor. We tested the efficacy of this PLA in Ctns(-/-) mice. We treated 12-month-old Ctns(-/-) mice and control mice with PLA (7 mg/kg/day, IP) or saline as a vehicle for 28 days. PLA normalized food intake and weight gain, increased fat and lean mass, decreased metabolic rate and improved muscle function. It also attenuated perturbations of energy homeostasis in adipose tissue and muscle in Ctns(-/-) mice. PLA attenuated adipose tissue browning in Ctns(-/-) mice. PLA increased gastrocnemius weight and fiber size as well as attenuated muscle fat infiltration in Ctns(-/-) mice. This was accompanied by correcting the increased expression of muscle wasting signaling while promoting the decreased expression of myogenesis in gastrocnemius of Ctns(-/-) mice. PLA attenuated aberrant expressed muscle genes that have been associated with muscle atrophy, increased energy expenditure and lipolysis in Ctns(-/-) mice. Leptin antagonism may represent a viable therapeutic strategy for adipose tissue browning and muscle wasting in INC.
Capozzi, F. ; Magkos, F. ; Fava, F. ; Milani, G. P. ; Agostoni, C. ; Astrup, A. ; Saguy, I. A Multidisciplinary Perspective of Ultra-Processed Foods and Associated Food Processing Technologies: A View of the Sustainable Road Ahead. NUTRIENTS 2021, 13.Abstract
Ultra-processed foods (UPFs) are negatively perceived by part of the scientific community, the public, and policymakers alike, to the extent they are sometimes referred to as not ``real food ``. Many observational surveys have linked consumption of UPFs to adverse health outcomes. This narrative synthesis and scientific reappraisal of available evidence aims to: (i) critically evaluate UPF-related scientific literature on diet and disease and identify possible research gaps or biases in the interpretation of data; (ii) emphasize the innovative potential of various processing technologies that can lead to modifications of the food matrix with beneficial health effects; (iii) highlight the possible links between processing, sustainability and circular economy through the valorisation of by-products; and (iv) delineate the conceptual parameters of new paradigms in food evaluation and classification systems. Although greater consumption of UPFs has been associated with obesity, unfavorable cardiometabolic risk factor profiles, and increased risk for non-communicable diseases, whether specific food processing techniques leading to ultra-processed formulations are responsible for the observed links between UPFs and various health outcomes remains elusive and far from being understood. Evolving technologies can be used in the context of sustainable valorisation of food processing by-products to create novel, low-cost UPFs with improved nutritional value and health potential. New paradigms of food evaluation and assessment should be funded and developed on several novel pillars-enginomics, signalling, and precision nutrition-taking advantage of available digital technologies and artificial intelligence. Research is needed to generate required scientific knowledge to either expand the current or create new food evaluation and classification systems, incorporating processing aspects that may have a significant impact on health and wellness, together with factors related to the personalization of foods and diets, while not neglecting recycling and sustainability aspects. The complexity and the predicted immense size of these tasks calls for open innovation mentality and a new mindset promoting multidisciplinary collaborations and partnerships between academia and industry.
Peri, A. ; Greenstein, E. ; Alon, M. ; Pai, J. A. ; Dingjan, T. ; Reich-Zeliger, S. ; Barnea, E. ; Barbolin, C. ; Levy, R. ; Arnedo-Pac, C. ; et al. Combined presentation and immunogenicity analysis reveals a recurrent RAS.Q61K neoantigen in melanoma. JOURNAL OF CLINICAL INVESTIGATION 2021, 131.Abstract
Neoantigens are now recognized drivers of the antitumor immune response. Recurrent neoantigens, shared among groups of patients, have thus become increasingly coveted therapeutic targets. Here, we report on the data-driven identification of a robustly presented, immunogenic neoantigen that is derived from the combination of HLA-A*01:01 and RAS.Q61K. Analysis of large patient cohorts indicated that this combination applies to 3% of patients with melanoma. Using HLA peptidomics, we were able to demonstrate robust endogenous presentation of the neoantigen in 10 tumor samples. We detected specific reactivity to the mutated peptide within tumor-infiltrating lymphocytes (TILs) from 2 unrelated patients, thus confirming its natural immunogenicity. We further investigated the neoantigen-specific clones and their T cell receptors (TCRs) via a combination of TCR sequencing, TCR overexpression, functional assays, and single-cell transcriptomics. Our analysis revealed a diverse repertoire of neoantigen-specific clones with both intra-and interpatient TCR similarities. Moreover, 1 dominant clone proved to cross-react with the highly prevalent RAS.Q61R variant. Transcriptome analysis revealed a high association of TCR clones with specific T cell phenotypes in response to cognate melanoma, with neoantigen-specific cells showing an activated and dysfunctional phenotype. Identification of recurrent neoantigens and their reactive TCRs can promote ``off-the shelf'' precision immunotherapies, alleviating limitations of personalized treatments.
Maurya, R. ; Sebastian, P. ; Namdeo, M. ; Devender, M. ; Gertler, A. COVID-19 Severity in Obesity: Leptin and Inflammatory Cytokine Interplay in the Link Between High Morbidity and Mortality. FRONTIERS IN IMMUNOLOGY 2021, 12.Abstract
Obesity is one of the foremost risk factors in coronavirus infection resulting in severe illness and mortality as the pandemic progresses. Obesity is a well-known predisposed chronic inflammatory condition. The dynamics of obesity and its impacts on immunity may change the disease severity of pneumonia, especially in acute respiratory distress syndrome, a primary cause of death from SARS-CoV-2 infection. The adipocytes of adipose tissue secret leptin in proportion to individuals' body fat mass. An increase in circulating plasma leptin is a typical characteristic of obesity and correlates with a leptin-resistant state. Leptin is considered a pleiotropic molecule regulating appetite and immunity. In immunity, leptin functions as a cytokine and coordinates the host's innate and adaptive responses by promoting the Th1 type of immune response. Leptin induced the proliferation and functions of antigen-presenting cells, monocytes, and T helper cells, subsequently influencing the pro-inflammatory cytokine secretion by these cells, such as TNF-alpha, IL-2, or IL-6. Leptin scarcity or resistance is linked with dysregulation of cytokine secretion leading to autoimmune disorders, inflammatory responses, and increased susceptibility towards infectious diseases. Therefore, leptin activity by leptin long-lasting super active antagonist's dysregulation in patients with obesity might contribute to high mortality rates in these patients during SARS-CoV-2 infection. This review systematically discusses the interplay mechanism between leptin and inflammatory cytokines and their contribution to the fatal outcomes in COVID-19 patients with obesity.
Schmid, C. ; Brockhoff, A. ; Ben Shoshan-Galeczki, Y. ; Kranz, M. ; Stark, T. D. ; Erkaya, R. ; Meyerhof, W. ; Niv, M. Y. ; Dawid, C. ; Hofmann, T. Comprehensive structure-activity-relationship studies of sensory active compounds in licorice (Glycyrrhiza glabra). FOOD CHEMISTRY 2021, 364.Abstract
Licorice saponins, the main constituents of Glycyrrhiza glabra L. roots, are highly appreciated by the consumer for their pleasant sweet and long lasting licorice taste. The objective of the present study was to understand the molecular features that contribute to bitter, sweet and licorice sensation of licorice roots, and whether individual compounds elicit more than one of these sensations. Therefore, a sensomics approach was conducted, followed by purification of the compounds with highest sensory impact, and by synthesis as well as full characterization via HRESIMS, ESIMS/MS and 1D/2D-NMR experiments. This led to the discovery and structure determination of 28 sweet, bitter and licorice tasting key phytochemicals, including two unknown compounds. A combination of sensorial, cell-based and computational analysis revealed distinct structural features, such as spatial arrangement of functional groups in the triterpenoid E-ring, driving to different taste sensations and sweet receptor hTAS1R2/ R3 stimulation.
Lotan, R. ; Ganmore, I. ; Livny, A. ; Itzhaki, N. ; Waserman, M. ; Shelly, S. ; Zacharia, M. ; Moshier, E. ; Uribarri, J. ; Beisswenger, P. ; et al. Effect of Advanced Glycation End Products on Cognition in Older Adults with Type 2 Diabetes: Results from a Pilot Clinical Trial. JOURNAL OF ALZHEIMERS DISEASE 2021, 82, 1785-1795.Abstract
Background: Dietary advanced glycation end-products (AGEs) are linked to cognitive decline. However, clinical trials have not tested the effect of AGEs on cognition in older adults. Objective: The aim of the current pilot trial was to examine the feasibility of an intervention to reduce dietary AGEs on cognition and on cerebral blood flow (CBF). Methods: The design is a pilot randomized controlled trial of dietary AGEs reduction in older adults with type 2 diabetes. Seventy-five participants were randomized to two arms. The control arm received standard of care (SOC) guidelines for good glycemic control; the intervention arm, in addition to SOC guidelines, were instructed to reduce their dietary AGEs intake. Global cognition and CBF were assessed at baseline and after 6 months of intervention. Results: At baseline, we found a reverse association between AGEs and cognitive functioning, possibly reflecting the long-term toxicity of AGEs on the brain. There was a significant improvement in global cognition at 6 months in both the intervention and SOC groups which was more prominent in participants with mild cognitive impairment. We also found that at baseline, higher AGEs were associated with increased CBF in the left inferior parietal cortex; however, 6 months of the AGEs lowering intervention did not affect CBF levels, despite lowering AGEs exposure in blood. Conclusion: The current pilot trial focused on the feasibility and methodology of intervening through diet to reduce AGEs in older adults with type 2 diabetes. Our results suggest that participants with mild cognitive impairment may benefit from an intensive dietary intervention.
Lotan, R. ; Ganmore, I. ; Livny, A. ; Shelly, S. ; Zacharia, M. ; Uribarri, J. ; Beisswenger, P. ; Cai, W. ; Beeri, M. S. ; Troen, A. M. Design and Feasibility of a Randomized Controlled Pilot Trial to Reduce Exposure and Cognitive Risk Associated With Advanced Glycation End Products in Older Adults With Type 2 Diabetes. FRONTIERS IN NUTRITION 2021, 8.Abstract
{{Introduction: Advanced glycation end products (AGEs) in diet and serum are positively correlated with chronic conditions such as type 2 diabetes and cognitive decline. Dietary reduction of AGEs was shown to reduce their level in serum and to have a beneficial effect on metabolic biomarkers. However, in part due to limitations of feasibility, clinical trials have not tested its effect on cognition in elderly. The current pilot study examines the feasibility of AGE reduction in elderly with diabetes in terms of recruitment and retention. Methods: The design is a randomized controlled pilot trial of dietary AGEs in elderly with type 2 diabetes ( NCT02739971). Recruitment followed two stages: we first recruited participants with mild cognitive impairment (MCI), and after expanding inclusion criteria, we later recruited cognitively normal participants with subjective memory complaints (SMCs). Participants were randomized to two arms. Participants in the control arm received standard of care (SOC) guidelines for good glycemic control; those in the experimental arm, in addition to SOC guidelines, were instructed to lower their dietary AGE intake, primarily by changing their cooking methods. Participants were closely followed for dietary adherence over 6 months and evaluated before and after the intervention for adherence to the assigned diet, blood tests, cognitive performance, and brain MRI. Results: Seventy-five participants (52 with MCI and 23 cognitively normal with SMCs) were recruited primarily through mass mailing and advertising in social media websites. Seventy participants finished the study, and dropout was similar in both groups (7.5% in control vs. 5.7% in intervention
Hintschich, C. A. ; Niv, M. Y. ; Hummel, T. The taste of the pandemic-contemporary review on the current state of research on gustation in coronavirus disease 2019 (COVID-19). INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY 2021.Abstract
Subjectively perceived impairment of taste is a common and distinct symptom of coronavirus disease 2019 (COVID-19). Large meta-analyses identified this symptom in approximately 50% of cases. However, this high prevalence is not supported by blinded and validated psychophysical gustatory testing, which showed a much lower prevalence in up to 26% of patients. This discrepancy may be due to misinterpretation of impaired retronasal olfaction as gustatory dysfunction. In addition, we hypothesized that COVID-19-associated hyposmia is involved in the decrease of gustatory function, as found for hyposmia of different origin. This indirect mechanism would be based on the central-nervous mutual amplification between the chemical senses, which fails in COVID-19-associated olfactory loss. However, further research is necessary on how severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) may directly impair the gustatory pathway as well as its subjective perception.
Israeli, H. ; Degtjarik, O. ; Fierro, F. ; Chunilal, V. ; Gill, A. K. ; Roth, N. J. ; Botta, J. ; Prabahar, V. ; Peleg, Y. ; Chan, L. F. ; et al. Structure reveals the activation mechanism of the MC4 receptor to initiate satiation signaling. SCIENCE 2021, 372, 808+.Abstract
Obesity is a global epidemic that causes morbidity and impaired quality of life. The melanocortin receptor 4 (MC4R) is at the crux of appetite, energy homeostasis, and body-weight control in the central nervous system and is a prime target for anti-obesity drugs. Here, we present the cryo-electron microscopy (cryo-EM) structure of the human MC4R-Gs signaling complex bound to the agonist setmelanotide, a cyclic peptide recently approved for the treatment of obesity. The work reveals the mechanism of MC4R activation, highlighting a molecular switch that initiates satiation signaling. In addition, our findings indicate that calcium (Ca2+) is required for agonist, but not antagonist, efficacy. These results fill a gap in the understanding of MC4R activation and could guide the design of future weight-management drugs.
Karni, N. ; Klein, H. ; Asseo, K. ; Benjamini, Y. ; Israel, S. ; Nammary, M. ; Olshtain-Pops, K. ; Nir-Paz, R. ; Hershko, A. ; Muszkat, M. ; et al. Self-Rated Smell Ability Enables Highly Specific Predictors of COVID-19 Status: A Case-Control Study in Israel. OPEN FORUM INFECTIOUS DISEASES 2021, 8.Abstract
Background. Clinical diagnosis of coronavirus disease 2019 (COVID-19) is essential to the detection and prevention of COVID-19. Sudden onset of loss of taste and smell is a hallmark of COVID-19, and optimal ways for including these symptoms in the screening of patients and distinguishing COVID-19 from other acute viral diseases should be established. Methods. We performed a case-control study of patients who were polymerase chain reaction-tested for COVID-19 (112 positive and 112 negative participants), recruited during the first wave (March 2020-May 2020) of the COVID-19 pandemic in Israel. Patients reported their symptoms and medical history by phone and rated their olfactory and gustatory abilities before and during their illness on a 1-10 scale. Results. Changes in smell and taste occurred in 68% (95% CI, 60%-76%) and 72% (95% CI, 64%-80%) of positive patients, with odds ratios of 24 (range, 11-53) and 12 (range, 6-23), respectively. The ability to smell was decreased by 0.5 +/- 1.5 in negatives and by 4.5 +/- 3.6 in positives. A penalized logistic regression classifier based on 5 symptoms had 66% sensitivity, 97% specificity, and an area under the receiver operating characteristics curve (AUC) of 0.83 on a holdout set. A classifier based on degree of smell change was almost as good, with 66% sensitivity, 97% specificity, and 0.81 AUC. The predictive positive value of this classifier was 0.68, and the negative predictive value was 0.97. Conclusions. Self-reported quantitative olfactory changes, either alone or combined with other symptoms, provide a specific tool for clinical diagnosis of COVID-19. A simple calculator for prioritizing COVID-19 laboratory testing is presented here. [GRAPHICS] .
Ron, I. ; Lerner, R. K. ; Rathaus, M. ; Livne, R. ; Ron, S. ; Barhod, E. ; Hemi, R. ; Tirosh, A. ; Strauss, T. ; Ofir, K. ; et al. The adipokine FABP4 is a key regulator of neonatal glucose homeostasis. JCI INSIGHT 2021, 6.Abstract
During pregnancy, fetal glucose production is suppressed, with rapid activation immediately postpartum. Fatty acid-binding protein 4 (FABP4) was recently demonstrated as a regulator of hepatic glucose production and systemic metabolism in animal models. Here, we studied the role of FABP4 in regulating neonatal glucose hemostasis. Serum samples were collected from pregnant women with normoglycemia or gestational diabetes at term, from the umbilical circulation, and from the newborns within 6 hours of life. The level of FABP4 was higher in the fetal versus maternal circulation, with a further rise in neonates after birth of approximately 3-fold. Neonatal FABP4 inversely correlated with blood glucose, with an approximately 10-fold increase of FABP4 in hypoglycemic neonates. When studied in mice, blood glucose of 12-hour-old WT, Fabp4(-/+), and Fabp4(-/-) littermate mice was 59 +/- 13 mg/dL, 50 +/- 11 mg/dL, and 43 +/- 11 mg/dL, respectively. Similar to our observations in humans, FABP4 levels in WT mouse neonates were approximately 8-fold higher compared with those in adult mice. RNA sequencing of the neonatal liver suggested altered expression of multiple glucagon-regulated pathways in Fabp4(-/-) mice. Indeed, Fabp4(-/-) liver glycogen was inappropriately intact, despite a marked hypoglycemia, with rapid restoration of normoglycemia upon injection of recombinant FABP4. Our data suggest an important biological role for the adipokine FABP4 in the orchestrated regulation of postnatal glucose metabolism.
Daniel, T. ; Ben-Shachar, M. ; Drori, E. ; Hamad, S. ; Permyakova, A. ; Ben-Cnaan, E. ; Tam, J. ; Kerem, Z. ; Rosenzweig, T. Grape pomace reduces the severity of non-alcoholic hepatic steatosis and the development of steatohepatitis by improving insulin sensitivity and reducing ectopic fat deposition in mice. JOURNAL OF NUTRITIONAL BIOCHEMISTRY 2021, 98.Abstract
While non-alcoholic fatty liver disease (NAFLD) represents the common cause of chronic liver disease, specific therapies are currently unavailable. The wine industry produces millions of tons of residue (pomace), which contains high levels of bioactive phytochemicals. The aim of this study was to clarify the potential benefits of grape pomace for the treatment of NAFLD at different levels of severity, and to clarify the mechanism of action. C57Bl/6 mice were given high fat diet (HFD) or western diet (WD) as models of obesity and hepatic steatosis or steatohepatitis, respectively, with or without pomace supplementation (50-250 mg/day). Pomace inhibited food intake, and reduced serum leptin and body weight gain. Ectopic fat deposition was reduced, while white adipose tissue mass was preserved. In addition, pomace improved glucose tolerance and insulin sensitivity, prevented the development of adipose tissue inflammation, and reduced hepatic steatosis. Higher expression of genes involved in fatty acids transport and oxidation was observed in adipose tissue, while lipogenic genes were attenuated in the liver of pomace-treated mice. In WD-fed mice, pomace reduced the severity of hepatic steatosis and inflammation and improved blood lipid profile, but was ineffective in reversing hepatic damage of advanced NASH. In conclusion, pomace improved insulin sensitivity and reduced ectopic fat deposition, leading to a healthier metabolic profile. Pomace may hold the potential as a supplement with beneficial health outcomes for the prevention and treatment of hepatic steatosis and other obesity-related pathologies. (c) 2021 Elsevier Inc. All rights reserved.
Dor, C. ; Stark, A. H. ; Dichtiar, R. ; Keinan-Boker, L. ; Shimony, T. ; Sinai, T. Milk and dairy consumption is positively associated with height in adolescents: results from the Israeli National Youth Health and Nutrition Survey. EUROPEAN JOURNAL OF NUTRITION 2021.Abstract
Purpose Milk consumption is associated with increased height primarily in early childhood. However, in adolescents, data are scarce with inconsistent results. Since height is a proxy for overall health and well-being, this study evaluated the association of dairy intake with height in adolescents. Methods Students in 7th-12th grades, participating in the 2015-2016 Israeli Health and Nutrition Youth Survey, a school-based cross-sectional study, completed self-administered questionnaires, including a semi-quantitative food frequency questionnaire (n = 3529, 48% males, 15.2 +/- 1.6 years). Anthropometric measurements were also performed. Dairy servings were calculated as the calcium equivalent of 1 cup of milk, and consumption was divided into four categories from very low (< 1 serving/day) to high (3 + servings/day). BMI- and Height-for-age z scores (HAZs) were calculated according to WHO growth standard; relatively short stature (RSS) was defined as HAZ < - 0.7 SD (< 25th percentile). Multivariable linear and logistic regression analyses were performed to evaluate the association of dairy intake with HAZ and prevalence of RSS, respectively. Results Median consumption of dairy products was 2 servings/day, 1.4 from unsweetened products (milk, cheese and yogurt). Controlling for age, sex, BMI-z-score and socioeconomic status, each increment of unsweetened dairy intake was associated with on average 0.04 higher HAZ (equivalent to 0.3-0.4 cm, p < 0.05), and with reduced risk for RSS: OR 0.90, 95%CI: 0.84, 0.97, p < 0.01. No such associations were found with sweetened dairy products. Conclusion Consumption of unsweetened dairy products (3-4 servings/day) appears to contribute to achieving growth potential in adolescents. Intervention studies are necessary to determine the causal relationship between dairy intake and linear growth.
Hutchings, C. ; Prokocimer Yair, Z. ; Reifen, R. ; Shemesh, M. Antimicrobial Effect of Zn2+ Ions Governs the Microbial Quality of Donor Human Milk. FOODS 2021, 10.Abstract
Donor human milk (HM) obtained at HM banks is exceptionally crucial for the feeding and treatment of preterm infants. Bacterial contaminations of HM in various stages of its handling are very common and can lead to disqualification of donations or severe infections in worse cases. Hence, HM donations are subject to strict bacteriological evaluations pre- and post-pasteurization. The main contaminating species vary between countries, banks and donors and even exhibit inter-individual variation. We initiated an assessment of the bacteriological composition of HM donated by women hospitalized in a neonatal intensive care unit in Israel. The most common bacterium identified was Staphylococcus epidermidis, found in all but one of the HM samples; the presence of several species of coagulase-negative Staphylococci was also noted. Next, we sought to develop a platform towards antibacterial treatment using Zn2+ ions that have recently been found to be potent against contaminants isolated from bovine milk. Zn2+ efficiently inhibited the growth of viable aerobic population and S. epidermidis in HM. Growth was also inhibited in other Gram-positive bacteria such as Bacillus cereus, a well-known food-borne pathogen. S. epidermidis and B. cereus cells grown in the presence of zinc were taken for microscopic evaluation, aiming to demonstrate zinc's antimicrobial mode of action morphologically. Images obtained using scanning electron microscopy indicated leakage of cellular content and cell lysis in S. epidermidis. Besides, B. cereus cells showed abnormalities in their cell surface and complete loss of flagella upon treatment with zinc. Along with the above findings, it should be noted that this was a pilot study that tested how high doses of Zn2+ affect breast milk as a product. Further research is likely needed on the safety of consumption of Zn2+-treated HM in infants and older children.
Xue, Y. ; Braslavsky, I. ; Quake, S. R. Temperature effect on polymerase fidelity. JOURNAL OF BIOLOGICAL CHEMISTRY 2021, 297.Abstract
The discovery of extremophiles helped enable the development of groundbreaking technology such as PCR. Temperature variation is often an essential step of these technology platforms, but the effect of temperature on the error rate of polymerases from different origins is underexplored. Here, we applied high-throughput sequencing to profile the error rates of DNA polymerases from psychrophilic, mesophilic, and thermophilic origins with single-molecule resolution. We found that the reaction temperature substantially increases substitution and deletion error rates of psychrophilic and mesophilic DNA polymerases. Our motif analysis shows that the substitution error profiles cluster according to phylogenetic similarity of polymerases, not the reaction temperature, thus suggesting that the reaction temperature increases the global error rate of polymerases independent of the sequence context. Intriguingly, we also found that the DNA polymerase I of psychrophilic bacteria exhibits higher polymerization activity than its mesophilic ortholog across all temperature ranges, including down to -19 degrees C, which is well below the freezing temperature of water. Our results provide a useful reference for how the reaction temperature, a crucial parameter of biochemistry, can affect DNA polymerase fidelity in organisms adapted to a wide range of thermal environments.
Rajasekharan, S. K. ; Paz-Aviram, T. ; Galili, S. ; Berkovich, Z. ; Reifen, R. ; Shemesh, M. Biofilm formation onto starch fibres byBacillus subtilisgoverns its successful adaptation to chickpea milk. MICROBIAL BIOTECHNOLOGY 2021, 14, 1839-1846.Abstract
Beneficial biofilms may confer effective adaptation to food matrices that assist bacteria in enduring hostile environmental conditions. The matrices, for instance, dietary fibres of various food products, might serve as a natural scaffold for bacterial cells to adhere and grow as biofilms. Here, we report on a unique interaction ofBacillus subtiliscells with the resistant starch fibresof chickpea milk (CPM), herein CPM fibres, along with the production of a reddish-pink pigment. Genetic analysis identified the pigment as pulcherrimin, and also revealed the involvement of Spo0A/SinI pathway in modulating the observed phenotypes. Besides, through successful colonization of the CPM fibres, the wild-type cells ofB. subtilisdisplayed enhanced survivability and resilience to environmental stress, such as heat andin vitrogastrointestinal treatments. In total, we infer that the biofilm formation on CPM fibres is an adaptation response ofB. subtilisfor strategic survival.
Jiao, S. ; Zhang, H. ; Liao, M. ; Hayouka, Z. ; Jing, P. Investigation of the potential direct and cross protection effects of sublethal injured Salmonella Typhimurium induced by radio frequency heating stress. FOOD RESEARCH INTERNATIONAL 2021, 150.Abstract
Many studies demonstrated that radio frequency (RF) was an effective pasteurization method for low-moisture foods (LMFs), and our previous study confirmed RF heating stress generated sublethal injured cells (SICs) of Salmonella enterica serovar Typhimurium (S. Typhimurium) in red pepper powder with initial aw >= 0.53. So this study investigated the potential direct protection and cross protection effects of the SICs of S. Typhimurium to multiple stresses, and analyzed fatty acid composition and cell morphology. Results showed that the SICs were repaired after incubating for 5 h, and there were no obvious direct and cross protection effects by exposing to different external stresses (heat, 15% ethanol, pH 3.0 acid buffer solution, 10% salt). According to the fatty acid composition analysis, no significant difference (p > 0.05) between the ratio of unsaturated to saturated fatty acids (UFA/SFA) was observed for SICs of S. Typhimurium and control cells, indicating the same membrane fluidity which can support the experimental results. This study investigated and confirmed there are no direct and cross protection effects for the SICs of S. Typhimurium induced by RF heating stress, and it would be helpful for deeply understand the response of pathogens under RF heating stress.
Sadhasivam, S. ; Barda, O. ; Zakin, V. ; Reifen, R. ; Sionov, E. Rapid Detection and Quantification of Patulin and Citrinin Contamination in Fruits. MOLECULES 2021, 26.Abstract
Patulin (PAT) and citrinin (CTN) are the most common mycotoxins produced by Penicillium and Aspergillus species and are often associated with fruits and fruit by-products. Hence, simple and reliable methods for monitoring these toxins in foodstuffs are required for regular quality assessment. In this study, we aimed to establish a cost-effective method for detection and quantification of PAT and CTN in pome fruits, such as apples and pears, using high-performance liquid chromatography (HPLC) coupled with spectroscopic detectors without the need for any clean-up steps. The method showed good performance in the analysis of these mycotoxins in apple and pear fruit samples with recovery ranges of 55-97% for PAT and 84-101% for CTN, respectively. The limits of detection (LOD) of PAT and CTN in fruits were 0.006 mu g/g and 0.001 mu g/g, while their limits of quantification (LOQ) were 0.018 mu g/g and 0.003 mu g/g, respectively. The present findings indicate that the newly developed HPLC method provides rapid and accurate detection of PAT and CTN in fruits.
Saibaba, G. ; Ruzal, M. ; Shinder, D. ; Yosefi, S. ; Druyan, S. ; Arazi, H. ; Froy, O. ; Sagi, D. ; Friedman-Einat, M. Time-Restricted Feeding in Commercial Layer Chickens Improves Egg Quality in Old Age and Points to Lack of Adipostat Activity in Chickens. FRONTIERS IN PHYSIOLOGY 2021, 12.Abstract
In mammals, time-restricted feeding (TRF) with no caloric restriction provides health benefits and extends longevity, usually with a minor (similar to 3%) or no reduction in total food consumption. In the current study, a TRF regimen of 6 h free access to food (08:00-14:00 h) was applied to Leghorn chickens from 25 to 86 weeks of age; control birds ate freely during the light hours (06:00-20:00 h). Unexpectedly, the TRF-treated birds consumed, on average, 11.7% less food than the controls. This was manifested by an average reduction of 9.6% in body weight, 2.6-fold in visceral fat accumulation, and 6.5% in egg weight. Hen-housed egg production was reduced by 3.6% in the TRF group compared with the control, along the first 40 weeks of the follow-up (P < 0.05), and changed into a tendency of 0.7% higher egg production thereafter. Several parameters of egg quality showed significant improvement (P < 0.05) in the TRF group compared with the controls. A comparison of diurnal patterns of feed consumption revealed a higher rate of hourly consumption in the TRF group and increased consumption before dark in the control group. In conclusion, the reduced feed intake in response to the TRF treatment and loss in visceral fat accumulation supports the lack of a strong adipostat activity in chickens and different appetite regulation mechanisms compared with mammals. Therefore, future TRF studies in chickens should be adjusted by extending the ad libitum time window. The lower feed intake by the TRF-treated chickens compared with the ad libitum-fed controls seems to reduce the efficiency of egg production. Nevertheless, the improved egg quality and persistence of egg lay at the older age suggest that similarly to mammals, the TRF treatment delayed at least some of the negative impacts associated with advanced age.