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Sugar has become embedded in modern food and beverages. This has led to overconsumption of sugar in children, adolescents, and adults, with more than 60 countries consuming more than four times (>100 g/person/day) the WHO recommendations (25 g/person/day). Recent evidence suggests that obesity and impulsivity from poor dietary habits leads to further overconsumption of processed food and beverages. The long-term effects on cognitive processes and hyperactivity from sugar overconsumption, beginning at adolescence are not known. Using a well-validated mouse model of sugar consumption, we found that long-term sugar consumption, at a level that significantly augments weight gain, elicits an abnormal hyperlocomotor response to novelty and alters both episodic and spatial memory. Our results are similar to those reported in attention deficit and hyperactivity disorders. The deficits in hippocampal-dependent learning and memory were accompanied by altered hippocampal neurogenesis, with an overall decrease in the proliferation and differentiation of newborn neurons within the dentate gyrus. This suggests that long-term overconsumption of sugar, as that which occurs in the Western Diet might contribute to an increased risk of developing persistent hyperactivity and neurocognitive deficits in adulthood., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Beecher, Alvarez Cooper, Wang, Walters, Chehrehasa, Bartlett and Belmer.)

Treatment for metastatic melanoma includes targeted and/or immunotherapy. Although many patients respond, only a subset has complete response. As late-stage patients often have multiple tumors in difficult access sites, non-invasive techniques are necessary for the development of predictive/prognostic biomarkers. PET/CT scans from 52 patients with stage III/IV melanoma were assessed and CT image parameters were evaluated as prognostic biomarkers. Analysis indicated patients with high standard deviation or high mean of positive pixels (MPP) had worse progression-free survival ( P = 0.00047 and P = 0.0014, respectively) and worse overall survival ( P = 0.0223 and P = 0.0465, respectively). Whole-exome sequencing showed high MPP was associated with BRAF mutation status ( P = 0.0389). RNA-sequencing indicated patients with immune "cold" signatures had worse survival, which was associated with CT biomarker, MPP4 ( P = 0.0284). Multiplex immunofluorescence confirmed a correlation between CD8 expression and image biomarkers ( P = 0.0028). IMPLICATIONS: CT parameters have the potential to be cost-effective biomarkers of survival in melanoma, and reflect the tumor immune-microenvironment. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/19/6/950/F1.large.jpg., (©2021 American Association for Cancer Research.)

The liver is positioned at the interface between two routes traversed by pathogens in disseminating infection. Whereas blood-borne pathogens are efficiently cleared in hepatic sinusoids by Kupffer cells (KCs), it is unknown how the liver prevents dissemination of peritoneal pathogens accessing its outer membrane. We report here that the hepatic capsule harbors a contiguous cellular network of liver-resident macrophages phenotypically distinct from KCs. These liver capsular macrophages (LCMs) were replenished in the steady state from blood monocytes, unlike KCs that are embryonically derived and self-renewing. LCM numbers increased after weaning in a microbiota-dependent process. LCMs sensed peritoneal bacteria and promoted neutrophil recruitment to the capsule, and their specific ablation resulted in decreased neutrophil recruitment and increased intrahepatic bacterial burden. Thus, the liver contains two separate and non-overlapping niches occupied by distinct resident macrophage populations mediating immunosurveillance at these two pathogen entry points to the liver., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Mycobacterium tuberculosis infection is characterized by a strong inflammatory response whereby a few infected macrophages within the granuloma induce sustained cellular accumulation. The mechanisms coordinating this response are poorly characterized. We hypothesized that microparticles (MPs), which are submicron, plasma membrane-derived vesicles released by cells under both physiological and pathological conditions, are involved in this process. Aerosol infection of mice with M. tuberculosis increased CD45(+) MPs in the blood after 4 wk of infection, and in vitro infection of human and murine macrophages with mycobacteria enhanced MP release. MPs derived from mycobacteria-infected macrophages were proinflammatory, and when injected into uninfected mice they induced significant neutrophil, macrophage, and dendritic cell recruitment to the injection site. When incubated with naive macrophages, these MPs enhanced proinflammatory cytokine and chemokine release, and they aided in the disruption of the integrity of a respiratory epithelial cell monolayer, providing a mechanism for the egress of cells to the site of M. tuberculosis infection in the lung. In addition, MPs colocalized with the endocytic recycling marker Rab11a within macrophages, and this association increased when the MPs were isolated from mycobacteria-infected cells. M. tuberculosis-derived MPs also carried mycobacterial Ag and were able to activate M. tuberculosis-specific CD4(+) T cells in vivo and in vitro in a dendritic cell-dependent manner. Collectively, these data identify an unrecognized role for MPs in host response against M. tuberculosis by promoting inflammation, intercellular communication, and cell migration.

Two-component signal transduction systems (2-CS) play an important role in bacterial pathogenesis. In the work presented here, we have studied the effects of a mutation in the Mycobacterium tuberculosis (Mtb) PhoPR 2-CS on the pathogenicity, physiology and global gene expression of this bacterial pathogen. Disruption of PhoPR causes a marked attenuation of growth in macrophages and mice and prevents growth in low-Mg2+ media. The inability to grow in THP-1 macrophages can be partially overcome by the addition of excess Mg2+ during infection. Global transcription assays demonstrate PhoP is a positive transcriptional regulator of several genes, but do not support the hypothesis that the Mtb PhoPR system is sensing Mg2+ starvation, as is the case with the Salmonella typhimurium PhoPQ 2-CS. The genes that were positively regulated include those found in the pks2 and the msl3 gene clusters that encode enzymes for the biosynthesis of sulphatides and diacyltrehalose and polyacyltrehalose respectively. Complementary biochemical studies, in agreement with recent results from another group, indicate that these complex lipids are also absent from the phoP mutant, and the lack of these components in its cell envelope may indirectly cause the mutant's high-Mg2+ growth requirement. The experiments reported here provide functional evidence for the PhoPR 2-CS involvement in Mtb pathogenesis, and they suggest that a major reason for the attenuation observed in the phoP mutant is the absence of certain complex lipids that are known to be important for virulence.

Coding statements of criminal suspects facilitated tests of four hypotheses about differences between behavioral cues to deception and the incriminating potential (IP) of the topic. Information from criminal investigations corroborated the veracity of 337 brief utterances from 28 videotaped confessions. A four-point rating of topic IP measured the degree of potential threat per utterance. Cues discriminating true vs. false comprised word/phrase repeats, speech disfluency spikes, nonverbal overdone, and protracted headshaking. Non-lexical sounds discriminated true vs. false in the reverse direction. Cues that distinguished IP only comprised speech speed, gesticulation amount, nonverbal animation level, soft weak vocal and "I (or we) just" qualifier. Adding "I don't know" to an answer discriminated both IP and true vs. false. The results supported hypothesis about differentiating deception cues from incriminating potential cues in high-stakes interviews, and suggested that extensive research on distinctions between stress-related cues and cues to deception would improve deception detection.

We tested isolates of Mycobacterium tuberculosis recovered from 117 patients for their susceptibilities to isoniazid (INH) and rifampin (RIF) by the Centers for Disease Control and Prevention's disk modification of the indirect method of proportions (MOP) test and a three-tube mycobacteria growth indicator tube (MGIT; BBL) antimycobacterial susceptibility test (AST). Sixty-seven of the M. tuberculosis isolates were recovered from Lowenstein-Jensen (BBL) subcultures, and 50 of the isolates were recovered from MGIT cultures of samples from various body sites. For the MGIT AST method, 0.5 ml of test organism suspension was inoculated into an MGIT with 0.1 micrograms of INH per ml, an MGIT with 1.0 micrograms of RIF per ml, and growth control MGIT. The tubes were incubated at 37 degrees C and were examined daily. The MGIT AST results were interpreted as follows: susceptible if the tubes containing INH or RIF did not fluoresce within 2 days of the time that the positive growth control fluoresced and resistant if the tubes containing INH or RIF did fluoresce within 2 days of the time that the positive growth control fluoresced. The mean time fluorescence for the positive growth control was 5.5 days. The two methods were in agreement for 114 of the 117 isolates from patients, while for 3 isolates there were minor discordant results.

Five hundred five blood samples for culture were processed in the Isolator lysis-centrifugation system and were then inoculated into a Mycobacteria Growth Indicator Tube (MGIT) and onto a Lowenstein-Jensen (L-J) slant. Forty-nine isolates of Mycobacterium avium complex and three isolates of Mycobacterium tuberculosis were recovered from 50 of the blood culture specimens. Forty-five isolates from 43 specimens were recovered in the MGIT, with a mean time to detection of 21 days. Forty-one isolates from 40 specimens were recovered in the L-J slants, and the mean time to detection was 36 days. Nine specimens were positive in the MGIT alone, while seven specimens were positive only in L-J medium.