Studies investigating the role that complex microbiotas associated with animals and humans play in health and wellbeing have been greatly facilitated by advances in DNA sequencing technology. Due to ...the still relatively high sequencing costs and the expense of establishing and running animal trials and collecting clinical samples, most of the studies reported in the literature are limited to a single trial and relatively small numbers of samples. Results from different laboratories, investigating similar trials and samples, have often produced quite different pictures of microbiota composition. This study investigated batch to batch variations in chicken cecal microbiota across three similar trials, represented by individually analysed samples from 207 birds. Very different microbiota profiles were found across the three flocks. The flocks also differed in the efficiency of nutrient use as indicated by feed conversion ratios. In addition, large variations in the microbiota of birds within a single trial were noted. It is postulated that the large variability in microbiota composition is due, at least in part, to the lack of colonisation of the chicks by maternally derived bacteria. The high hygiene levels maintained in modern commercial hatcheries, although effective in reducing the burden of specific diseases, may have the undesirable effect of causing highly variable bacterial colonization of the gut. Studies in humans and other animals have previously demonstrated large variations in microbiota composition when comparing individuals from different populations and from different environments but this study shows that even under carefully controlled conditions large variations in microbiota composition still occur.
We consider “twin supergravities”-pairs of supergravities with N+ and N− supersymmetries, N+>N−, with identical bosonic sectors-in the context of tensoring super Yang-Mills multiplets. It is ...demonstrated that the pairs of twin supergravity theories are related through their left and right super Yang-Mills factors. This procedure generates new theories from old ones. In particular, the matter coupled N− twins in D=3, 5, 6 and the N−=1 twins in D=4 have not, as far as we are aware, been obtained previously using the double-copy construction, adding to the growing list of double-copy constructible theories. The use of fundamental matter multiplets in the double-copy construction leads us to introduce a bifundamental scalar that couples to the well-known biadjoint scalar field. It is also shown that certain matter coupled supergravities admit more than one factorization into left and right super Yang-Mills-matter theories.
Background
Streptococcus gallolyticus subspecies gallolyticus
(SGG) and
Fusobacterium (F.) nucleatum
have been implicated in colorectal carcinogenesis. Here, the association of immune responses to ...bacterial exposure with advancing stages of colorectal neoplasia was assessed by multiplex serology.
Methods
Immunoglobulin (Ig) A and G antibody responses to eleven proteins each of
F. nucleatum
and SGG were measured in plasma of controls (
n
= 100) and patients with colorectal cancer (CRC,
n
= 25), advanced adenoma (
n
= 82), or small polyps (
n
= 85). Multivariable logistic regression was used to evaluate the association of bacterial sero-positivity with colorectal neoplasia. In a cohort subset with matched data (
n
= 45),
F. nucleatum
sero-positivity was correlated with bacterial abundance in both neoplastic and matched normal tissue.
Results
IgG sero-positivity to Fn1426 of
F. nucleatum
was associated with an increased CRC risk (OR = 4.84; 95% CI 1.46–16.0), while IgA sero-positivity to any SGG protein or specifically Gallo0272 and Gallo1675 alone was associated with increased advanced adenoma occurrence (OR = 2.02, 95% CI 1.10–3.71; OR = 2.67, 95% CI 1.10–6.46; and OR = 6.17, 95% CI 1.61–23.5, respectively). Only
F. nucleatum
abundance in the normal mucosa positively correlated with the IgA response to the Fn1426 antigen (Correlation coefficient (r) = 0.38,
p
< 0.01).
Conclusion
Antibody responses to SGG and
F. nucleatum
were associated with occurrence of colorectal adenomas and CRC, respectively. Further studies are needed to clarify the role these microbes or the immune response to their antigens may have in colorectal carcinogenesis stages.
Graphical Abstract
Numerous individual differences, models, and measures have been associated with the 'emotional intelligence' (EI) label. This paper discusses one of the most pervasive problems regarding EI-related ...individual differences, namely, the lack of a meaningful theoretical framework. First, drawing upon existing theoretical frameworks, we argue that EI-related characteristics can be considered constituents of existing models of cognitive ability (ability EI), personality (trait EI), and emotion regulation (EI competencies). Second, having differentiated between these perspectives (ability, personality, and emotion regulation), we draw upon existing theory and research to build the Integrated Model of Affect-related Individual Differences (IMAID), which provides an initial mechanistic representation that explains how the different EI-related constructs are likely to interrelate and coalesce to influence affective outcomes. In essence, the IMAID is an integrated mediation model in which emotion regulation mediates the effects of ability EI and affect-related personality traits upon outcomes. Viewing EI-related constructs as interrelated extensions of well-established individual difference frameworks clarifies some pervasive misconceptions regarding EI-related characteristics and provides scholars and practitioners with a clear and useful theoretical framework ripe for exploration. We conclude by using the IMAID to suggest a theoretically driven agenda for future research.
Background The receptor for advanced glycation end products (RAGE) shares common ligands and signaling pathways with TLR4, a key mediator of house dust mite ( Dermatophagoides pteronyssinus ) (HDM) ...sensitization. We hypothesized that RAGE and its ligand high-mobility group box-1 (HMGB1) cooperate with TLR4 to mediate HDM sensitization. Objectives To determine the requirement for HMGB1 and RAGE, and their relationship with TLR4, in airway sensitization. Methods TLR4−/− , RAGE−/− , and RAGE-TLR4−/− mice were intranasally exposed to HDM or cockroach ( Blatella germanica ) extracts, and features of allergic inflammation were measured during the sensitization or challenge phase. Anti-HMGB1 antibody and the IL-1 receptor antagonist Anakinra were used to inhibit HMGB1 and the IL-1 receptor, respectively. Results The magnitude of allergic airway inflammation in response to either HDM or cockroach sensitization and/or challenge was significantly reduced in the absence of RAGE but not further diminished in the absence of both RAGE and TLR4. HDM sensitization induced the release of HMGB1 from the airway epithelium in a biphasic manner, which corresponded to the sequential activation of TLR4 then RAGE. Release of HMGB1 in response to cockroach sensitization also was RAGE dependent. Significantly, HMGB1 release occurred downstream of TLR4-induced IL-1α, and upstream of IL-25 and IL-33 production. Adoptive transfer of HDM-pulsed RAGE+/+ dendritic cells to RAGE−/− mice recapitulated the allergic responses after HDM challenge. Immunoneutralization of HMGB1 attenuated HDM-induced allergic airway inflammation. Conclusion The HMGB1-RAGE axis mediates allergic airway sensitization and airway inflammation. Activation of this axis in response to different allergens acts to amplify the allergic inflammatory response, which exposes it as an attractive target for therapeutic intervention.
The COVID-19 pandemic continues to ravage the world, with the United States being highly affected. A vaccine provides the best hope for a permanent solution to controlling the pandemic. However, to ...be effective, a vaccine must be accepted and used by a large majority of the population. The aim of this study was to understand the attitudes towards and obstacles facing vaccination with a potential COVID-19 vaccine. To measure these attitudes a survey was administered to 316 respondents across the United States by a survey corporation. Structural equation modeling was used to analyze the relationships of several factors with attitudes toward potential COVID-19 vaccination. Prior vaccine usage and attitudes predicted attitudes towards COVID-19 vaccination. Assessment of the severity of COVID-19 for the United States was also predictive. Approximately 68% of all respondents were supportive of being vaccinated for COVID-19, but side effects, efficacy and length of testing remained concerns. Longer testing, increased efficacy and development in the United States were significantly associated with increased vaccine acceptance. Messages promoting COVID-19 vaccination should seek to alleviate the concerns of those who are already vaccine-hesitant. Messaging directed at the benefits of vaccination for the United States as a country would address the second predictive factor. Enough time should be taken to allay concerns about both short- and long-term side effects before a vaccine is released.
By regarding gravity as the convolution of left and right Yang-Mills theories together with a spectator scalar field in the biadjoint representation, we derive in linearized approximation, the ...gravitational symmetries of general covariance, p-form gauge invariance, local Lorentz invariance, and local supersymmetry from the flat space Yang-Mills symmetries of local gauge invariance and global super-Poincaré symmetry. As a concrete example, we focus on the new minimal (12+12) off shell version of simple four-dimensional supergravity obtained by tensoring the off shell Yang-Mills multiplets (4+4, N_{L}=1) and (3+0, N_{R}=0).
Identification of bacteria associated with desirable productivity outcomes in animals may offer a direct approach to the identification of probiotic bacteria for use in animal production. We ...performed three controlled chicken trials (n = 96) to investigate caecal microbiota differences between the best and poorest performing birds using four performance measures; feed conversion ratio (FCR), utilization of energy from the feed measured as apparent metabolisable energy, gain rate (GR), and amount of feed eaten (FE). The shifts in microbiota composition associated with the performance measures were very different between the three trials. Analysis of the caecal microbiota revealed that the high and low FCR birds had significant differences in the abundance of some bacteria as demonstrated by shifts in microbiota alpha and beta diversity. Trials 1 and 2 showed significant overall community shifts, however, the microbial changes driving the difference between good and poor performers were very different. Lachnospiraceae, Ruminococcaceae, and Erysipelotrichaceae families and genera Ruminococcus, Faecalibacterium and multiple lineages of genus Clostridium (from families Lachnospiraceae, Ruminococcaceae, and Erysipelotrichaceae) were highly abundant in good FCR birds in Trial 1. Different microbiota was associated with FCR in Trial 2; Catabacteriaceae and unknown Clostridiales family members were increased in good FCR and genera Clostridium (from family Clostridiaceae) and Lactobacillus were associated with poor FCR. Trial 3 had only mild microbiota differences associated with all four performance measures. Overall, the genus Lactobacillus was correlated with feed intake which resulted in poor FCR performance. The genus Faecalibacterium correlated with improved FCR, increased GR and reduced FE. There was overlap in phylotypes correlated with improved FCR and GR, while different microbial cohorts appeared to be correlated with FE. Even under controlled conditions different cohorts of birds developed distinctly different microbiotas. Within the different trial groups the abundance of certain bacterial groups correlated with productivity outcomes. However, with different underlying microbiotas there were different bacteria correlated with performance. The challenge will be to identify probiotic bacteria that can reliably deliver favorable outcomes from diverse microbiotas.
Enzyme-catalyzed reactions have begun to transform pharmaceutical manufacturing, offering levels of selectivity and tunability that can dramatically improve chemical synthesis. Combining enzymatic ...reactions into multistep biocatalytic cascades brings additional benefits. Cascades avoid the waste generated by purification of intermediates. They also allow reactions to be linked together to overcome an unfavorable equilibrium or avoid the accumulation of unstable or inhibitory intermediates. We report an in vitro biocatalytic cascade synthesis of the investigational HIV treatment islatravir. Five enzymes were engineered through directed evolution to act on non-natural substrates. These were combined with four auxiliary enzymes to construct islatravir from simple building blocks in a three-step biocatalytic cascade. The overall synthesis requires fewer than half the number of steps of the previously reported routes.
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