Miracle-dz/UniFAR-FTUs huggingface dataset:
Gathered produce in Zimbabwe's communal areas changing resource availability and use

This article analyses the relationship between environmental change and the availability and use of gathered produce in one of Zimbabwe's deforested communal areas. Based on a series of interviews with households of different socio‐economic status, it investigates the shifting contribution to rural livelihoods and diet made by gathered products such as fruit, nuts, leaf vegetables, mushrooms, insects, rodents and leaf litter. Species favouring arable and disturbed environments have become more abundant, whereas those flourishing in woodlands have diminished. There is no simple relationship between changing resource availability and shifting patterns of consumption and sale of gathered produce: socio‐economic changes and changing preferences are important influences on consumption, whereas the emergence of markets for gathered resources is related to processes of specialization and exchange rather than physical scarcity. There has been an overall decrease in the diversity of gathered produce eaten, with in.
Hemolysin of Uropathogenic Escherichia coli Evokes Extensive Shedding of the Uroepithelium and Hemorrhage in Bladder Tissue within the First 24 Hours after Intraurethral Inoculation of Mice

ABSTRACT Many uropathogenic Escherichia coli (UPEC) strains produce both hemolysin (Hly) and cytotoxic necrotizing factor type 1 (CNF1), and the loci for these toxins are often linked. The conclusion that Hly and CNF1 contribute to urovirulence is supported by the results of epidemiological studies associating the severity of urinary tract infections (UTIs) with toxin production by UPEC isolates. Additionally, we previously reported that mouse bladders and rat prostates infected with UPEC strain CP9 exhibit a more profound inflammatory response than the organs from animals challenged with CP9cnf1 and that CNF1 decreases the antimicrobial activities of polymorphonuclear leukocytes. More recently, we created an Hly mutant, CP9ΔhlyA1::cat, and showed that it was less hemolytic and destructive for cultured bladder cells than CP9 was. Here we evaluated the relative effects of mutations in hlyA1 or cnf1 alone or together on the pathogenicity of CP9 in a mouse model of ascending UTI. To do this, we constructed an hlyA1-complemented clone of CP9ΔhlyA1::cat and an hlyA1cnf1 CP9 double mutant. We found that Hly had no influence on bacterial colonization of the bladder or kidneys in single or mixed infections with the wild type and CP9ΔhlyA1::cat but that it did provoke sloughing of the uroepithelium and bladder hemorrhage within the first 24 h after challenge. Finally, we confirmed that CNF1 expression induces bladder inflammation and, in particular, as shown in this study, submucosal edema. From these data, we speculate that Hly and CNF1 may be largely responsible for the signs and symptoms of cystitis in humans infected with toxigenic UPEC.
Salmonella enterica Serovar Typhimurium Pathogenicity Island 1-Encoded Type III Secretion System Translocases Mediate Intimate Attachment to Nonphagocytic Cells

ABSTRACT Delivery of bacterial proteins into mammalian cells by type III secretion systems (TTSS) is thought to require the intimate association of bacteria with target cells. The molecular bases of this intimate association appear to be different in different bacteria involving TTSS components, as well as surface determinants not associated with TTSS. We show here that the protein translocases SipB, SipC, and SipD of the Salmonella enterica serovar Typhimurium pathogenicity island 1 (SPI-1)-encoded TTSS are required for the intimate association of these bacteria with mammalian cells. S. Typhimurium mutant strains lacking any of the translocases were defective for intimate attachment. Immunofluorescence microscopy showed that SipD is present on the bacterial surface prior to bacterial contact with host cells. In contrast, SipB and SipC were detected on the bacterial surface only subsequent to bacterial contact with the target cell. We conclude that the coordinated deployment and interaction between the protein translocases mediate the SPI-1 TTSS-dependent intimate association of S. Typhimurium with host cells.
Multi-Instance Deep Learning: Discover Discriminative Local Anatomies for Bodypart Recognition

In general image recognition problems, discriminative information often lies in local image patches. For example, most human identity information exists in the image patches containing human faces. The same situation stays in medical images as well. “Bodypart identity” of a transversal slice-which bodypart the slice comes from-is often indicated by local image information, e.g., a cardiac slice and an aorta arch slice are only differentiated by the mediastinum region. In this work, we design a multi-stage deep learning framework for image classification and apply it on bodypart recognition. Specifically, the proposed framework aims at: 1) discover the local regions that are discriminative and non-informative to the image classification problem, and 2) learn a image-level classifier based on these local regions. We achieve these two tasks by the two stages of learning scheme, respectively. In the pre-train stage, a convolutional neural network (CNN) is learned in a multi-instance learning fashion to extract the most discriminative and and non-informative local patches from the training slices. In the boosting stage, the pre-learned CNN is further boosted by these local patches for image classification. The CNN learned by exploiting the discriminative local appearances becomes more accurate than those learned from global image context. The key hallmark of our method is that it automatically discovers the discriminative and non-informative local patches through multi-instance deep learning. Thus, no manual annotation is required. Our method is validated on a synthetic dataset and a large scale CT dataset. It achieves better performances than state-of-the-art approaches, including the standard deep CNN.
Classification of CAM Use and Its Correlates in Patients With Early-Stage Breast Cancer

Hypothesis: Self-reported use of complementary and alternative medicine (CAM) has been shown to increase following a cancer diagnosis, and breast cancer survivors are the heaviest users among cancer survivors. The aim of this study was to determine whether the prevalence estimate of CAM use varied according to classification of CAM. The authors used a comprehensive system to classify CAM users and test differences in demographic, lifestyle, quality of life, and cancer characteristics among them. Study design and methods: Participants were 2562 breast cancer survivors participating in the Women’s Healthy Eating and Living (WHEL) Study, aged 28 to 74 years. A structured telephone interview assessed CAM use, questioning about specific CAM practices, and whether use was related to cancer. This study examined CAM use in relation to demographics, health behaviors, and quality of life. Results: Approximately 80% of the women used CAM for general purposes but only 50% reported CAM use for cancer purposes. Visual imagery, spiritual healing, and meditation were the most frequently used practices for cancer purposes. CAM use, defined as consulting a CAM practitioner and regular use, was significantly related to younger age, higher education, increased fruit and vegetable intake, and lower body mass index (P < .05). CAM users who had seen a practitioner were also more likely to report poor physical and mental health than non-CAM users (P < .05). CAM use was not associated with changes in physical and mental health between study baseline and 1-year follow-up. Conclusion: This study addressed important differences in the classification of CAM use among breast cancer survivors. Future studies need to further test the potential benefits and risks associated with CAM use.
Identification of Signaling Pathways by Which CD40 Stimulates Autophagy and Antimicrobial Activity against Toxoplasma gondii in Macrophages

ABSTRACT CD40 is an important stimulator of autophagy and autophagic killing of Toxoplasma gondii in host cells. In contrast to autophagy induced by nutrient deprivation or pattern recognition receptors, less is known about the effects of cell-mediated immunity on Beclin 1 and ULK1, key regulators of autophagy. Here we studied the molecular mechanisms by which CD40 stimulates autophagy in macrophages. CD40 ligation caused biphasic Jun N-terminal protein kinase (JNK) phosphorylation. The second phase of JNK phosphorylation was dependent on autocrine production of tumor necrosis factor alpha (TNF-α). TNF-α and JNK signaling were required for the CD40-induced increase in autophagy. JNK signaling downstream of CD40 caused Ser-87 phosphorylation of Bcl-2 and dissociation between Bcl-2 and Beclin 1, an event known to stimulate the autophagic function of Beclin 1. However, TNF-α alone was unable to stimulate autophagy. CD40 also stimulated autophagy via a pathway that included calcium/calmodulin-dependent kinase kinase β (CaMKKβ), AMP-activated protein kinase (AMPK), and ULK1. CD40 caused AMPK phosphorylation at its activating site, Thr-172. This effect was mediated by CaMKKβ and was not impaired by neutralization of TNF-α. CD40 triggered AMPK-dependent Ser-555 phosphorylation of ULK1. CaMKKβ, AMPK, and ULK1 were required for CD40-induced increase in autophagy. CD40-mediated autophagic killing of Toxoplasma gondii is known to require TNF-α. Knockdown of JNK, CaMKKβ, AMPK, or ULK1 prevented T. gondii killing in CD40-activated macrophages. The second phase of JNK phosphorylation—Bcl-2 phosphorylation—Bcl-2–Beclin 1 dissociation and AMPK phosphorylation-ULK1 phosphorylation occurred simultaneously at ∼4 h post-CD40 stimulation. Thus, CaMKKβ and TNF-α are upstream molecules by which CD40 acts on ULK1 and Beclin 1 to stimulate autophagy and killing of T. gondii.
Mechanisms of Cardioprotective Effect of Aged Garlic Extract Against Doxorubicin-Induced Cardiotoxicity

Aged garlic has been extensively studied and has been shown to have a number of medicinal properties, including immunomodulatory, hepatoprotective, antimutagenic, anticarcinogenic, and antioxidant effects. The objective of this study was to investigate the mechanisms of the cardioprotective effect of aged garlic extract (AGE), a widely used herbal medicine with potent antioxidant activity, against doxorubicin-induced cardiotoxicity. Moreover, the study investigated if the cardioprotective effect of AGE might be at the expense of the antitumor effect of the anticancer drug doxorubicin (DOX). Primary cultured neonatal rat cardiac myocytes were treated with DOX, AGE, and their combination for 24 hours. DOX increased p53 and caspase 3 activity–induced apoptotic cell death, whereas AGE pretreatment suppressed the action of DOX. AGE pretreatment did not interfere with the cytotoxic activity of DOX, but it increased the DOX uptake into tumor cells and increased the long term survivors of tumor-bearing mice from 30% to 70%. In conclusion, DOX impairs viability of cardiac myocytes, at least partially by activating the p53-mediated apoptotic signaling. AGE can effectively and extensively counteract this action of DOX and may potentially protect the heart from severe toxicity of DOX. At the same time, AGE did not interfere with antitumor activity of DOX.
Green Tea and Lung Cancer

Background: Green tea is a beverage widely used by lung cancer patients and the public for its purported anticancer properties. The authors conducted a systematic review of green tea for the treatment and prevention of lung cancer. Methodology: Six electronic databases were searched from inception until November 2011 for human interventional and preclinical evidence pertaining to the safety and efficacy of green tea for lung cancer. Results: A total of 84 articles met inclusion criteria: two Phase I trials, three reports of one surrogate study, and 79 preclinical studies. There is a lack of controlled trials investigating green tea for lung cancer. Two Phase I studies showed no objective tumor responses at the maximum tolerated dose, ranging from 3 to 4.2 g/m2 green tea extract (GTE) per day. Four cups of green tea daily decreased DNA damage (8OH-dG) in smokers. Human studies indicate that 800mg of green tea catechins daily does not alter activity of the CYP2D6, CYP1A2, CYP3A4 and CYP2C9 enzymes, however in vitro evidence suggests that green tea may bind to and reduce the effectiveness of bortezomib. Green tea applied topically may improve the healing time of radiation burns. Conclusions: Although some evidence suggests that chemopreventative benefits can be accrued from green tea, there is currently insufficient evidence to support green tea as a treatment or preventative agent for lung cancer. Green tea should not be used by patients on bortezomib therapy. Further research is warranted to explore this natural agent for lung cancer treatment and prevention.
Identification of In Vivo-Induced Antigens Including an RTX Family Exoprotein Required for Uropathogenic Escherichia coli Virulence

ABSTRACT Uncomplicated urinary tract infections (UTI) are caused most commonly by uropathogenic Escherichia coli (UPEC). Whole-genome screening approaches, including transcriptomic, proteomic, and signature-tagged mutagenesis, have shown that UPEC highly expresses or requires genes for translational machinery, capsule, lipopolysaccharide, type 1 fimbriae, and iron acquisition systems during UTI. To identify additional genes expressed by UPEC during UTI, an immunoscreening approach termed in vivo-induced antigen technology (IVIAT) was employed to identify antigens produced during experimental infection that are not produced during in vitro culture. An inducible protein expression library, constructed from genomic DNA isolated from UPEC strain CFT073, was screened using exhaustively adsorbed pooled sera from 20 chronically infected female CBA/J mice. Using this approach, we identified 93 antigens induced by UPEC in vivo. A representative subset of these genes was tested by quantitative PCR for expression by CFT073 in vivo and during growth in human urine or LB medium in vitro; proWX, narJI, lolA, lolD, tosA (upxA), c2432, katG, ydhX, kpsS, and yddQ were poorly expressed in vitro but highly expressed in vivo. Of these, tosA, a gene encoding a predicted repeat-in-toxin family member, was expressed exclusively during UTI. Deletion of tosA in UPEC strain CFT073 resulted in significant attenuation in bladder and kidney infections during ascending UTI. By screening for in vivo-induced antigens, we identified a novel UPEC virulence factor and additional proteins that could be useful as potential vaccine targets.
Albumin Inhibits Pseudomonas aeruginosa Quorum Sensing and Alters Polymicrobial Interactions

ABSTRACT Polymicrobial interactions are complex and can influence the course of an infection, as is the case when two or more species exhibit a synergism that produces a disease state not seen with any of the individual species alone. Cell-to-cell signaling is key to many of these interactions, but little is understood about how the host environment influences polymicrobial interactions or signaling between bacteria. Chronic wounds are typically polymicrobial, with Staphylococcus aureus and Pseudomonas aeruginosa being the two most commonly isolated species. While P. aeruginosa readily kills S. aureusin vitro, the two species can coexist for long periods together in chronic wound infections. In this study, we investigated the ability of components of the wound environment to modulate interactions between P. aeruginosa and S. aureus. We demonstrate that P. aeruginosa quorum sensing is inhibited by physiological levels of serum albumin, which appears to bind and sequester some homoserine lactone quorum signals, resulting in the inability of P. aeruginosa to produce virulence factors that kill S. aureus. These data could provide important clues regarding the virulence of P. aeruginosa in albumin-depleted versus albumin-rich infection sites and an understanding of the nature of friendly versus antagonistic interactions between P. aeruginosa and S. aureus.
Effect of Conjugated Linoleic Acid Supplementation on Inflammatory Factors and Matrix Metalloproteinase Enzymes in Rectal Cancer Patients Undergoing Chemoradiotherapy

Objectives. The aims of this study were to determine the effect of conjugated linoleic acid (CLA) supplementation on inflammatory factors and matrix metalloproteinase (MMP) enzymes in rectal cancer patients undergoing chemoradiothetrapy. Method and Material. In this randomized, double-blind, placebo-controlled pilot study, 34 volunteer patients with rectal cancer undergoing chemoradiotherapy assigned into the CLA group (n = 16), receiving 3 g CLA/d, and placebo group (n = 18) receiving placebo capsules (sunflower oil) for 6 weeks. The supplementation began 1 week before starting RT (loading period) and continued every day during treatment. Before and after intervention, serum tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), IL-6, MMP-2, MMP-9, and high-sensitivity C-reactive protein (hsCRP) were measured by enzyme-linked immunosorbent assay (ELISA) kits and immunoturbidimetric method, respectively. Independent t tests and paired t tests were used to compare parameters between and within groups, respectively. Results. In the CLA group, the mean serum TNF-α, IL-1β, hsCRP, MMP-9, and MMP-2 levels reduced insignificantly. However, significant changes in TNF-α (P = 0.04), hsCRP (P = 0.03), and MMP-9 (P = 0.04) concentrations were observed in the CLA group when compared with the placebo group. The mean serum IL-6 level remained unchanged in the CLA group but increased remarkably in the placebo group. Conclusion. According to our results, CLA supplementation improved inflammatory factors, MMP-2, and MMP-9 as biomarkers of angiogenesis and tumor invasion. It seems that CLA may provide new complementary treatment by reducing tumor invasion and resistance to cancer treatment in patients with rectal cancer.
Position of O-Acetylation within the Capsular Repeat Unit Impacts the Biological Properties of Pneumococcal Serotypes 33A and 33F

ABSTRACT Streptococcus pneumoniae (pneumococcus) produces many capsule types that differ in their abilities to evade host immune recognition. To explain these serotype-dependent protective capacities, many studies have investigated capsular thickness or the interaction of the capsule with complement proteins, but the effects of small chemical modifications of the capsule on its function have not been studied. One small chemical modification found frequently among pneumococcal capsules is O-acetylation. Pneumococcal serotype 33A has two membrane-bound O-acetyltransferase genes, wciG and wcjE. A 33A wcjE-deficient variant, 33F, occurs naturally and is increasing in prevalence in the wake of widespread conjugate vaccine use, but no wciG-deficient variants have been reported. To study the biological consequence of the loss of O-acetylation, we created wciG-deficient variants in both serotypes 33A and 33F, which we named 33X1 (ΔwciG) and 33X2 (ΔwciG ΔwcjE). Serotypes 33X1 and 33X2 express novel capsule types based on serological and biochemical analyses. We found that loss of WcjE-mediated O-acetylation appears not to affect cell wall shielding, since serotypes 33A and 33F exhibit comparable nonspecific opsonophagocytic killing, biofilm production, and adhesion to nasopharyngeal cells, though serotype 33F survived short-term drying better than serotype 33A. Loss of WciG-mediated O-acetylation in serotypes 33X1 and 33X2, however, resulted in a phenotype resembling that of nonencapsulated strains: increased cell wall accessibility, increased nonspecific opsonophagocytic killing, enhanced biofilm formation, and increased adhesion to nasopharyngeal cells. We conclude that WciG-mediated, but not WcjE-mediated, O-acetylation is important for producing protective capsules in 33A and that small chemical changes to the capsule can drastically affect its biological properties.
Spatial, Temporal, and Functional Assessment of LC3-Dependent Autophagy in Shigella flexneri Dissemination

Shigella flexneri disseminates within the colonic mucosa by displaying actin-based motility in the cytosol of epithelial cells. Motile bacteria form membrane protrusions that project into adjacent cells and resolve into double-membrane vacuoles (DMVs) from which the bacteria escape, thereby achieving cell-to-cell spread. ABSTRACT Shigella flexneri disseminates within the colonic mucosa by displaying actin-based motility in the cytosol of epithelial cells. Motile bacteria form membrane protrusions that project into adjacent cells and resolve into double-membrane vacuoles (DMVs) from which the bacteria escape, thereby achieving cell-to-cell spread. During dissemination, S. flexneri is targeted by LC3-dependent autophagy, a host cell defense mechanism against intracellular pathogens. The S. flexneri type III secretion system effector protein IcsB was initially proposed to counteract the recruitment of the LC3-dependent autophagy machinery to cytosolic bacteria. However, a recent study proposed that LC3 was recruited to bacteria in DMVs formed during cell-to-cell spread. To resolve the controversy and clarify the role of autophagy in S. flexneri infection, we tracked dissemination using live confocal microscopy and determined the spatial and temporal recruitment of LC3 to bacteria. This approach demonstrated that (i) LC3 was exclusively recruited to wild-type or icsB bacteria located in DMVs and (ii) the icsB mutant was defective in cell-to-cell spread due to failure to escape LC3-positive as well as LC3-negative DMVs. Failure of S. flexneri to escape DMVs correlated with late LC3 recruitment, suggesting that LC3 recruitment is the consequence and not the cause of DMV escape failure. Inhibition of autophagy had no positive impact on the spreading of wild-type or icsB mutant bacteria. Our results unambiguously demonstrate that IcsB is required for DMV escape during cell-to-cell spread, regardless of LC3 recruitment, and do not support the previously proposed notion that autophagy counters S. flexneri dissemination.
Bistable Expression of CsgD in Salmonella enterica Serovar Typhimurium Connects Virulence to Persistence

ABSTRACT Pathogenic bacteria often need to survive in the host and the environment, and it is not well understood how cells transition between these equally challenging situations. For the human and animal pathogen Salmonella enterica serovar Typhimurium, biofilm formation is correlated with persistence outside a host, but the connection to virulence is unknown. In this study, we analyzed multicellular-aggregate and planktonic-cell subpopulations that coexist when S. Typhimurium is grown under biofilm-inducing conditions. These cell types arise due to bistable expression of CsgD, the central biofilm regulator. Despite being exposed to the same stresses, the two cell subpopulations had 1,856 genes that were differentially expressed, as determined by transcriptome sequencing (RNA-seq). Aggregated cells displayed the characteristic gene expression of biofilms, whereas planktonic cells had enhanced expression of numerous virulence genes. Increased type three secretion synthesis in planktonic cells correlated with enhanced invasion of a human intestinal cell line and significantly increased virulence in mice compared to the aggregates. However, when the same groups of cells were exposed to desiccation, the aggregates survived better, and the competitive advantage of planktonic cells was lost. We hypothesize that CsgD-based differentiation is a form of bet hedging, with single cells primed for host cell invasion and aggregated cells adapted for persistence in the environment. This allows S. Typhimurium to spread the risks of transmission and ensures a smooth transition between the host and the environment.