The geographic and temporal origins of the domestic dog remain controversial, as genetic data suggest a domestication process in East Asia beginning 15,000 years ago, whereas the oldest doglike ...fossils are found in Europe and Siberia and date to >30,000 years ago. We analyzed the mitochondrial genomes of 18 prehistoric canids from Eurasia and the New World, along with a comprehensive panel of modern dogs and wolves. The mitochondrial genomes of all modern dogs are phylogenetically most closely related to either ancient or modern canids of Europe. Molecular dating suggests an onset of domestication there 18,800 to 32,100 years ago. These findings imply that domestic dogs are the culmination of a process that initiated with European hunter-gatherers and the canids with whom they interacted.
In the framework of a 3-3-1 model with right-handed neutrinos and three scalar triplets we consider different spontaneous symmetry breaking patterns seeking for a non-linear realization of accidental ...symmetries of the model, which will produce physical Nambu–Goldstone (NG) bosons in the neutral scalar spectrum. We make a detailed study of the safety of the model concerning the NG boson emission in energy-loss processes which could affect the standard evolution of astrophysical objects. We consider the model with a
Z
2
symmetry, conventionally used in the literature, finding that in all of the symmetry breaking patterns the model is excluded. Additionally, looking for solutions for that problem, we introduce soft
Z
2
-breaking terms in the scalar potential in order to remove the extra accidental symmetries and at the same time maintain the model as simple as possible. We find that there is only one soft
Z
2
-breaking term that enables us to get rid of the problematic NG bosons.
In this work we present a common framework for neutrino masses and dark matter. Specifically, we work with a local B - L extension of the standard model which has three right-handed neutrinos, n(Ri), ...and some extra scalars, Phi, phi(i), besides the standard model fields. The n(Ri)'s have nonstandard B - L quantum numbers and thus these couple to different scalars. This model has the attractive property that an almost automatic Z(2) symmetry acting only on a fermionic field, n(R3), is present. Taking advantage of this Z(2) symmetry, we study both the neutrino mass generation via a natural seesaw mechanism at low energy and the possibility of n(R3) being a dark matter candidate. For this last purpose, we study its relic abundance and its compatibility with the current direct detection experiments.
CTCF is a haploinsufficient tumour suppressor gene with diverse normal functions in genome structure and gene regulation. However the mechanism by which CTCF haploinsufficiency contributes to cancer ...development is not well understood. CTCF is frequently mutated in endometrial cancer. Here we show that most CTCF mutations effectively result in CTCF haploinsufficiency through nonsense-mediated decay of mutant transcripts, or loss-of-function missense mutation. Conversely, we identified a recurrent CTCF mutation K365T, which alters a DNA binding residue, and acts as a gain-of-function mutation enhancing cell survival. CTCF genetic deletion occurs predominantly in poor prognosis serous subtype tumours, and this genetic deletion is associated with poor overall survival. In addition, we have shown that CTCF haploinsufficiency also occurs in poor prognosis endometrial clear cell carcinomas and has some association with endometrial cancer relapse and metastasis. Using shRNA targeting CTCF to recapitulate CTCF haploinsufficiency, we have identified a novel role for CTCF in the regulation of cellular polarity of endometrial glandular epithelium. Overall, we have identified two novel pro-tumorigenic roles (promoting cell survival and altering cell polarity) for genetic alterations of CTCF in endometrial cancer.
Water limitation is an important determinant of the distribution, abundance and diversity of plant species. Yet, little is known about how the response to limiting water supply changes among closely ...related plant species with distinct ecological preferences. Comparison of the model annual species Arabidopsis thaliana with its close perennial relatives A. lyrata and A. halleri, can help disentangle the molecular and physiological changes contributing to tolerance and avoidance mechanisms, because these species must maintain tolerance and avoidance mechanisms to increase long-term survival, but they are exposed to different levels of water stress and competition in their natural habitat.
A dry-down experiment was conducted to mimic a period of missing precipitation. The covariation of a progressive decrease in soil water content (SWC) with various physiological and morphological plant traits across a set of representative genotypes in A. thaliana, A. lyrata and A. halleri was quantified. Transcriptome changes to soil dry-down were further monitored.
The analysis of trait covariation demonstrates that the three species differ in the strategies they deploy to respond to drought stress. Arabidopsis thaliana showed a drought avoidance reaction but failed to survive wilting. Arabidopsis lyrata efficiently combined avoidance and tolerance mechanisms. In contrast, A. halleri showed some degree of tolerance to wilting but it did not seem to protect itself from the stress imposed by drought. Transcriptome data collected just before plant wilting and after recovery corroborated the phenotypic analysis, with A. lyrata and A. halleri showing a stronger activation of recovery- and stress-related genes, respectively.
The response of the three Arabidopsis species to soil dry-down reveals that they have evolved distinct strategies to face drought stress. These strategic differences are in agreement with the distinct ecological priorities of the stress-tolerant A. lyrata, the competitive A. halleri and the ruderal A. thaliana.
There is evidence that maternal milieu and changes in environmental factors during the prenatal period may exert a lasting impact on the brain health of the newborn, even in case of neonatal brain ...hypoxia-ischemia (HI). The present study aimed to investigate the effects of maternal environmental enrichment (EE) on HI-induced energetic and metabolic failure, along with subsequent neural cell responses in the early postnatal period. Male Wistar pups born to dams exposed to maternal EE or standard conditions (SC) were randomly divided into Sham-SC, HI-SC, Sham-EE, and HI-EE groups. Neonatal HI was induced on postnatal day (PND) 3. The Na+,K+-ATPase activity, mitochondrial function and neuroinflammatory related-proteins were assessed at 24 h and 48 h after HI. MicroPET-FDG scans were used to measure glucose uptake at three time points: 24 h post-HI, PND18, and PND24. Moreover, neuronal preservation and glial cell responses were evaluated at PND18. After HI, animals exposed to maternal EE showed an increase in Na+,K+-ATPase activity, preservation of mitochondrial potential/mass ratio, and a reduction in mitochondrial swelling. Glucose uptake was preserved in HI-EE animals from PND18 onwards. Maternal EE attenuated HI-induced cell degeneration, white matter injury, and reduced astrocyte immunofluorescence. Moreover, the HI-EE group exhibited elevated levels of IL-10 and a reduction in Iba-1 positive cells. Data suggested that the regulation of AKT/ERK1/2 signaling pathways could be involved in the effects of maternal EE. This study evidenced that antenatal environmental stimuli could promote bioenergetic and neural resilience in the offspring against early HI damage, supporting the translational value of pregnancy-focused environmental treatments.
•Maternal EE prevented HI-induced mitochondrial, Na+,K+-ATPase, and metabolic impairments, preserving cell energy function.•Maternal EE regulates AKT/ERK1/2 signaling pathways, offering a potential mechanism for its protective effects.•Maternal EE restored glucose uptake, interhemispheric connectivity, and maintained neuronal and oligodendrocyte populations.•Maternal EE induced an anti-inflammatory response as supported by increased IL-10 levels and reduced Iba-1 positive cells.•The hippocampus and parietal cortex bear notably distinct responses to neonatal EE and maternal EE experiences.
Breast reconstruction is an important element in the successful therapy of breast cancer 1. Thereby, autologous microvascular breast reconstruction has been shown to be a reliable technique. The use ...of a deep inferior epigastric perforator (DIEP) flap or a muscle-sparing (MS) free transverse rectus abdominis musculocutaneous (TRAM) flap is recognized in many centres as gold standard for reconstructive options 2–4. Based on our experiences with 137 patients over a 5-year period we want to highlight the technical aspects of the free microsurgical autologous breast reconstruction using a DIEP flap.
Between 01/2013 and 12/2017 we treated 137 patients (age 32–78 years, mean age 52 years) after mastectomy with autologous microsurgical free flap breast reconstruction. A DIEP flap was used for breast reconstruction in 33 patients. In 104 cases, we performed a muscle sparing TRAM flap. In this video we demonstrate the typical sequence of operative steps of a DIEP flap in a 32 year old patient after mastectomy due to an invasive ductal breast carcinoma.
The rate of total flap loss in our department was 2.2% including all patients. In less than 1%, partial flap necrosis could be observed. 61% of the patients had undergone previous irradiation. Within the small number of flap loss, we could not observe a trend towards a correlation between flap loss and previous irradiation.
Autologous breast reconstruction using a DIEP or MS-TRAM flap provides a surgically safe technique including a low incidence of flap loss in specialized centres.
•Breast reconstruction is an important element in the successful therapy of breast cancer.•Autologous breast reconstruction using the DIEP or MS-TRAM flap provides a surgically safe technique.•Assessing flap perfusion using intra-operative indocyanine green (ICG) fluorescence angiography.
SummaryIntroductionA presumed association between more severe lower urinary tract symptoms (LUTS) and more severe functional constipation (FC) remains unconfirmed. Because the Rome IV criteria do not ...quantify FC, an adult constipation scoring system was modified and adapted for use in children. ObjectivesThe objective of this study was to assess the correlation between FC severity as determined by the modified constipation scoring system and LUTS severity in children/adolescents and the correlation between this modified scoring system and the Rome IV criteria. Study designThis was a cross-sectional study including 5- to 17-year-old patients with LUTS, with or without FC. Patients with neurological and/or anatomical abnormalities of the genitourinary and/or gastrointestinal tract were excluded. Girls with Dysfunctional Voiding Symptom Score (DVSS) ≥6 and boys with DVSS ≥9 were diagnosed with lower urinary tract dysfunction (LUTD). Patients with at least two positive Rome IV criteria were considered constipated. The severity of FC according to the adapted constipation scoring system was classified as mild for scores of 1–10, moderate for scores 11–20, and severe for scores 21–30. ResultsOf 128 patients with LUTS, 71 (55.5%) were female. Lower urinary tract dysfunction was detected in 107 patients (83.6%) and was more common in girls. Functional constipation was present in 80 patients (62.5%). Constipated children had higher constipation scores and DVSS, with both scores increasing with the severity of FC. Correlation was moderate between the constipation score and the DVSS (þ = 0.5, p < 0.001) and was strong between positivity for a greater number of Rome IV criteria and the constipation score (þ = 0.7, p < 0.001). Most of the constipated patients had mild or moderate FC, while in 30 non-constipated patients, the constipation score indicated mild FC. DiscussionPatients from a specialist center are more likely to have more severe medical problems, and this may have influenced the correlation between the scores. The modifications made to the constipation scoring system require a future validation study. Nevertheless, this study provides new data on urinary dysfunction and its association with FC and highlights the need to investigate occult bowel symptoms that could affect the treatment of urinary dysfunction. ConclusionThe intensity of FC as measured by the modified constipation scoring system correlated with the severity of the urinary symptoms in children/adolescents with LUTS/LUTD. In constipated patients, there was a correlation between the modified constipation scoring system and the Rome IV criteria. In non-constipated patients, the constipation scoring system identified symptoms/signs of bowel dysfunction not picked up by the Rome IV criteria. Finally, constipation score modified for use in children and adolescents could be important for research purpose and particularly having a prognostic importance. Summary Fig.Box showing the constipation scoring system adapted for children. Summary Fig.
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