Ipsographing the Dubject; or, The Contradictions of Twitter

Precise control of self-renewal and differentiation of progenitor cells into the cranial neural crest (CNC) pool ensures proper head development, guided by signaling pathways such as BMPs, FGFs, Shh and Notch. Here, we show that murine Sox2 plays an essential role in controlling progenitor cell behavior during craniofacial development. A "Conditional by Inversion" Sox2 allele (Sox2(COIN) ) has been employed to generate an epiblast ablation of Sox2 function (Sox2(EpINV) ). Sox2 (EpINV/+(H)) haploinsufficient and conditional (Sox2(EpINV/mosaic) ) mutant embryos proceed beyond gastrulation and die around E11. These mutant embryos exhibit severe anterior malformations, with hydrocephaly and frontonasal truncations, which could be attributed to the deregulation of CNC progenitor cells during their epithelial to mesenchymal transition. This irregularity results in an exacerbated and aberrant migration of Sox10(+) NCC in the branchial arches and frontonasal process of the Sox2 mutant embryos. These results suggest a novel role for Sox2 as a regulator of the epithelial to mesenchymal transitions (EMT) that are important for the cell flow in the developing head

Long-lived charged Higgs at LHC as a probe of scalar Dark Matter

We study inert charged Higgs boson $H^\pm$ production and decays at LHC experiments in the context of constrained scalar dark matter model (CSDMM). In the CSDMM the inert doublet and singlet scalar's mass spectrum is predicted from the GUT scale initial conditions via RGE evolution. We compute the cross sections of processes $pp\to H^+H^-,\, H^\pm S_i^0$ at the LHC and show that for light $H^\pm$ the first one is dominated by top quark mediated 1-loop diagram with Higgs boson in s-channel. In a significant fraction of the parameter space $H^\pm$ are long-lived because their decays to predominantly singlet scalar dark matter (DM) and next-to-lightest (NL) scalar, $H^\pm\to S_{\text{DM, NL}} ff',$ are suppressed by the small singlet-doublet mixing angle and by the moderate mass difference $\Delta M=M_{H^+}-M_{\text{DM}} .$ The experimentally measurable displaced vertex in $H^\pm$ decays to leptons and/or jets and missing energy allows one to discover the $H^+H^-$ signal over the huge $W^+W^-$ background. We propose benchmark points for studies of this scenario at the LHC. If, however, $H^\pm$ are short-lived, the subsequent decays $S_{\text{NL}}\to S_{\text{DM}} f\bar f$ necessarily produce additional displaced vertices that allow to reconstruct the full $H^\pm$ decay chain.Comment: 15 pages, 5 figure

UV friendly T-parity in the SU(6)/Sp(6) little Higgs model

Electroweak precision tests put stringent constraints on the parameter space of little Higgs models. Tree-level exchange of TeV scale particles in a generic little Higgs model produce higher dimensional operators that make contributions to electroweak observables that are typically too large. To avoid this problem a discrete symmetry dubbed T-parity can be introduced to forbid the dangerous couplings. However, it was realized that in simple group models such as the littlest Higgs model, the implementation of T-parity in a UV completion could present some challenges. The situation is analogous to the one in QCD where the pion can easily be defined as being odd under a new $Z_2$ symmetry in the chiral Lagrangian, but this $Z_2$ is not a symmetry of the quark Lagrangian. In this paper we examine the possibility of implementing a T-parity in the low energy $SU(6)/Sp(6)$ model that might be easier to realize in the UV. In our model, the T-parity acts on the low energy non-linear sigma model field in way which is different to what was originally proposed for the Littlest Higgs, and lead to a different low energy theory. In particular, the Higgs sector of this model is a inert two Higgs doublets model with an approximate custodial symmetry. We examine the contributions of the various sectors of the model to electroweak precision data, and to the dark matter abundance.Comment: 21 pages,4 figures. Clarifications added, typos corrected and references added. Published in JHE

Bacterial DNAemia in Older Participants and Nonagenarian Offspring and Association With Redox Biomarkers: Results From MARK-AGE Study

Aging and age-related diseases have been linked to microbial dysbiosis with changes in blood bacterial DNA concentration. This condition may promote chronic low-grade inflammation, which can be further aggravated by antioxidant nutrient deficiency. Low plasma carotenoids are associated with an increased risk of inflammation and cellular damage and predict mortality. However, no evidence is yet available on the relationship between antioxidants and the blood bacterial DNA (BB-DNA). Therefore, this study aimed to compare BB-DNA from (a) GO (nonagenarian offspring), (b) age-matched controls (Randomly recruited Age-Stratified Individuals from the General population [RASIG]), and (c) spouses of GO (SGO) recruited in the MARK-AGE project, as well as to investigate the association between BB-DNA, behavior habits, Charlson Comorbidity Index (CCI), leucocyte subsets, and the circulating levels of some antioxidants and oxidative stress markers. BB-DNA was higher in RASIG than GO and SGO, whereas GO and SGO participants showed similar values. BB-DNA increased in smokers and males with CCI >= 2 compared with those with CCI <= 1 within RASIG. Moreover, BB-DNA was positively associated with lymphocyte, neutrophil, and monocyte counts, but not with self-reported dietary habits. Higher quartiles of BB-DNA were associated with low lutein and zeaxanthin and elevated malondialdehyde plasma concentrations in RASIG. BB-DNA was also positively correlated with nitric oxide levels. Herein, we provide evidence of a reduced BB-DNA in individuals from long-living families and their spouses, suggesting a decreased microbial dysbiosis and bacterial systemic translocation. BB-DNA was also associated with smoking, CCI, leukocyte subsets, and some redox biomarkers in older participants

Association between fat-soluble vitamins and self-reported health status: A cross-sectional analysis of the MARK-AGE cohort

Self-rated health (SRH) is associated with higher risk of death. Since low plasma levels of fat-soluble vitamins are related to mortality, we aimed to assess whether plasma concentrations of vitamins A, D and E were associated with SRH in the MARK-AGE study. We included 3158 participants (52% female) aged between 35-75 years. Cross-sectional data were collected via questionnaires. An enzyme immunoassay quantified 25-hydroxyvitamin D and HPLC determined α-tocopherol and retinol plasma concentrations. The median 25-hydroxyvitamin D and retinol concentrations differed significantly (P<0.001) between SRH categories, and were lower in the combined fair/poor category versus the excellent, very good, good categories (25-hydroxvitamin D: 40.8 vs. 51.9, 49.3, 46.7 nmol/l, respectively; retinol: 1.67 vs. 1.75, 1.74, 1.70 μmol/l, respectively). Both vitamin D and retinol status were independently associated with fair/poor SRH in multiple regression analyses: adjusted ORs (95% CI) for the vitamin D insufficiency, deficiency, severe deficiency categories were 1.33 (1.06-1.68), 1.50 (1.17-1.93), and 1.83 (1.34-2.50) respectively; P=0.015, P=0.001, P<0.001, and for the second/third/fourth retinol quartiles: 1.44 (1.18-1.75), 1.57 (1.28-1.93), 1.49 (1.20-1.84); all P<0.001. No significant associations were reported for α-tocopherol quartiles. Lower vitamin A and D status emerged as independent markers for fair/poor SRH. Further insights into the long-term implications of these modifiable nutrients on health status are warranted

Association of Torquetenovirus Viremia with Physical Frailty and Cognitive Impairment in Three Independent European Cohorts

Introduction: Immunosenescence and inflammaging have been implicated in the pathophysiology of frailty. Torquetenovirus (TTV), a single-stranded DNA anellovirus, the major component of the human blood virome, shows an increased replication rate with advancing age. An elevated TTV viremia has been associated with an impaired immune function and an increased risk of mortality in the older population. The objective of this study was to analyze the relation between TTV viremia, physical frailty, and cognitive impairment. Methods: TTV viremia was measured in 1,131 nonfrail, 45 physically frail, and 113 cognitively impaired older adults recruited in the MARK-AGE study (overall mean age 64.7 ± 5.9 years), and then the results were checked in two other independent cohorts from Spain and Portugal, including 126 frail, 252 prefrail, and 141 nonfrail individuals (overall mean age: 77.5 ± 8.3 years). Results: TTV viremia ≥4log was associated with physical frailty (OR: 4.69; 95% CI: 2.06-10.67, p < 0.0001) and cognitive impairment (OR: 3.49, 95% CI: 2.14-5.69, p < 0.0001) in the MARK-AGE population. The association between TTV DNA load and frailty status was confirmed in the Spanish cohort, while a slight association with cognitive impairment was observed (OR: 1.33; 95% CI: 1.000-1.773), only in the unadjusted model. No association between TTV load and frailty or cognitive impairment was found in the Portuguese sample, although a negative association between TTV viremia and MMSE score was observed in Spanish and Portuguese females. Conclusions: These findings demonstrate an association between TTV viremia and physical frailty, while the association with cognitive impairment was observed only in the younger population from the MARK-AGE study. Further research is necessary to clarify TTV's clinical relevance in the onset and progression of frailty and cognitive decline in older individuals

Time-restricted feeding improves adaptation to chronically alternating light-dark cycles

Disturbance of the circadian clock has been associated with increased risk of cardio-metabolic disorders. Previous studies showed that optimal timing of food intake can improve metabolic health. We hypothesized that time-restricted feeding could be a strategy to minimize long term adverse metabolic health effects of shift work and jetlag. In this study, we exposed female FVB mice to weekly alternating light-dark cycles (i.e. 12 h shifts) combined with ad libitum feeding, dark phase feeding or feeding at a fixed clock time, in the original dark phase. In contrast to our expectations, long-term disturbance of the circadian clock had only modest effects on metabolic parameters. Mice fed at a fixed time showed a delayed adaptation compared to ad libitum fed animals, in terms of the similarity in 24 h rhythm of core body temperature, in weeks when food was only available in the light phase. This was accompanied by increased plasma triglyceride levels and decreased energy expenditure, indicating a less favorable metabolic state. On the other hand, dark phase feeding accelerated adaptation of core body temperature and activity rhythms, however, did not improve the metabolic state of animals compared to ad libitum feeding. Taken together, restricting food intake to the active dark phase enhanced adaptation to shifts in the light-dark schedule, without significantly affecting metabolic parameters