Genetic and Epigenetic Influences on Cutaneous Cellular Senescence

Skin is the largest human organ system, and its protective function is critical to survival. The epithelial, dermal, and subcutaneous compartments are heterogeneous mixtures of cell types, yet they all display age-related skin dysfunction through the accumulation of an altered phenotypic cellular state called senescence. Cellular senescence is triggered by complex and dynamic genetic and epigenetic processes. A senescence steady state is achieved in different cell types under various and overlapping conditions of chronological age, toxic injury, oxidative stress, replicative exhaustion, DNA damage, metabolic dysfunction, and chromosomal structural changes. These inputs lead to outputs of cell-cycle withdrawal and the appearance of a senescence-associated secretory phenotype, both of which accumulate as tissue pathology observed clinically in aged skin. This review details the influence of genetic and epigenetic factors that converge on normal cutaneous cellular processes to create the senescent state, thereby dictating the response of the skin to the forces of both intrinsic and extrinsic aging. From this work, it is clear that no single biomarker or process leads to senescence, but that it is a convergence of factors resulting in an overt aging phenotype

The Co-occurrence of child and intimate partner maltreatment in the family: characteristics of the violent perpetrators

This study considers the characteristics associated with mothers and fathers who maltreat their child and each other in comparison to parents who only maltreat their child. One hundred and sixty-two parents who had allegations of child maltreatment made against them were considered. The sample consisted of 43 fathers (Paternal Family—PF) and 23 mothers (Maternal Family—MF) who perpetrated both partner and child maltreatment, together with 23 fathers (Paternal Child—PC) and 26 mothers (Maternal Child—MC) who perpetrated child maltreatment only. In addition, 2 fathers (Paternal Victim—PV) and 23 mothers (Maternal Victim—MV) were victims of intimate partner maltreatment and perpetrators of child maltreatment and 7 fathers (Paternal Non-abusive Carer—PNC) and 15 mothers (Maternal Non-abusive Carer—MNC) did not maltreat the child but lived with an individual who did. Within their family unit, 40.7% of parents perpetrated both intimate partner and child maltreatment. However, fathers were significantly more likely to maltreat both their partner and child than mothers and mothers were significantly more likely to be victims of intimate partner violence than fathers. PF fathers conducted the highest amount of physical and/or sexual child maltreatment while MC and MV mothers perpetrated the highest amount of child neglect. Few significant differences between mothers were found. PF fathers had significantly more factors associated with development of a criminogenic lifestyle than PC fathers. Marked sex differences were demonstrated with PF fathers demonstrating significantly more antisocial characteristics, less mental health problems and fewer feelings of isolation than MF mothers. MC mothers had significantly more childhood abuse, mental health problems, parenting risk factors and were significantly more likely to be biologically related to the child than PC fathers. This study suggests that violent families should be assessed and treated in a holistic manner, considering the effects of partner violence upon all family members, rather than exclusively intervening with the violent man

Specialist antenatal clinics for women at high risk of preterm birth: a systematic review of qualitative and quantitative research

Background Preterm birth (PTB) is the leading cause of perinatal morbidity and mortality. Women with previous prenatal loss are at higher risk of preterm birth. A specialist antenatal clinic is considered as one approach to improve maternity and pregnancy outcomes. Methods A systematic review of quantitative, qualitative and mixed method studies conducted on women at high risk of preterm birth (PTB). The review primary outcomes were to report on the specialist antenatal clinics effect in preventing or reducing preterm birth, perinatal mortality and morbidity and women’s perceptions and experiences of a specialist clinic whether compared or not compared with standard antenatal care. Other secondary maternal, infant and economic outcomes were also determined. A comprehensive search strategy was carried out in English within electronic databases as far back as 1980. The reviewers selected studies, assessed the quality, and extracted data independently. Results were summarized and tabulated. Results Eleven studies fully met the review inclusion criteria, ten were quantitative design studies and only one was a qualitative design study. No mixed method design study was included in the review. All were published after 1989, seven were conducted in the USA and four in the UK. Results from five good to low quality randomised controlled trials (RCTs), all conducted before 1990, did not illustrate the efficacy of the clinic in reducing preterm birth. Whereas results from more recent low quality cohort studies showed some positive neonatal outcomes. Themes from one good quality qualitative study reflected on the emotional and psychological need to reduce anxiety and stress of women referred to such a clinic. Women expressed their negative emotional responses at being labelled as high risk and positive responses to being assessed and treated in the clinic. Women also reported that their partners were struggling to cope emotionally. Conclusions Findings from this review were mixed. Evidence from cohort studies indicated a specialist clinic may be a means of predicting or preventing preterm birth. Testing this in a randomised controlled trial is desirable, though may be hard to achieve due to the growing focus of such clinics on managing women at high risk of preterm birth. Ongoing research has to recognize women’s experiences and perceptions of such a clinic. Further clarification of the optimal referral route and a clear and standardized management and cost economic evaluation plan are also required. Fathers support and experience of PTB clinics should also be included in further research

Abbot Ice Shelf, structure of the Amundsen Sea continental margin and the southern boundary of the Bellingshausen Plate seaward of West Antarctica

Inversion of NASA Operation IceBridge airborne gravity over the Abbot Ice Shelf in West Antarctica for subice bathymetry defines an extensional terrain made up of east-west trending rift basins formed during the early stages of Antarctica/Zealandia rifting. Extension is minor, as rifting jumped north of Thurston Island early in the rifting process. The Amundsen Sea Embayment continental shelf west of the rifted terrain is underlain by a deeper, more extensive sedimentary basin also formed during rifting between Antarctica and Zealandia. A well-defined boundary zone separates the mildly extended Abbot extensional terrain from the deeper Amundsen Embayment shelf basin. The shelf basin has an extension factor, b, of 1.5–1.7 with 80–100 km of extension occurring across an area now 250 km wide. Following this extension, rifting centered north of the present shelf edge and proceeded to continental rupture. Since then, the Amundsen Embayment continental shelf appears to have been tectonically quiescent and shaped by subsidence, sedimentation, and the advance and retreat of the West Antarctic Ice Sheet. The Bellingshausen Plate was located seaward of the Amundsen Sea margin prior to incorporation into the Antarctic Plate at about 62 Ma. During the latter part of its independent existence, Bellingshausen plate motion had a clockwise rotational component relative to Antarctica producing convergence across the north-south trending Bellingshausen Gravity Anomaly structure at 94°W and compressive deformation on the continental slope between 94°W and 102°W. Farther west, the relative motion was extensional along an east-west trending zone occupied by the Marie Byrd Seamounts

Multimodal surface-based morphometry reveals diffuse cortical atrophy in traumatic brain injury.

<p>Abstract</p> <p>Background</p> <p>Patients with traumatic brain injury (TBI) often present with significant cognitive deficits without corresponding evidence of cortical damage on neuroradiological examinations. One explanation for this puzzling observation is that the diffuse cortical abnormalities that characterize TBI are difficult to detect with standard imaging procedures. Here we investigated a patient with severe TBI-related cognitive impairments whose scan was interpreted as normal by a board-certified radiologist in order to determine if quantitative neuroimaging could detect cortical abnormalities not evident with standard neuroimaging procedures.</p> <p>Methods</p> <p>Cortical abnormalities were quantified using multimodal surfaced-based morphometry (MSBM) that statistically combined information from high-resolution structural MRI and diffusion tensor imaging (DTI). Normal values of cortical anatomy and cortical and pericortical DTI properties were quantified in a population of 43 healthy control subjects. Corresponding measures from the patient were obtained in two independent imaging sessions. These data were quantified using both the average values for each lobe and the measurements from each point on the cortical surface. The results were statistically analyzed as z-scores from the mean with a p < 0.05 criterion, corrected for multiple comparisons. False positive rates were verified by comparing the data from each control subject with the data from the remaining control population using identical statistical procedures.</p> <p>Results</p> <p>The TBI patient showed significant regional abnormalities in cortical thickness, gray matter diffusivity and pericortical white matter integrity that replicated across imaging sessions. Consistent with the patient's impaired performance on neuropsychological tests of executive function, cortical abnormalities were most pronounced in the frontal lobes.</p> <p>Conclusions</p> <p>MSBM is a promising tool for detecting subtle cortical abnormalities with high sensitivity and selectivity. MSBM may be particularly useful in evaluating cortical structure in TBI and other neurological conditions that produce diffuse abnormalities in both cortical structure and tissue properties.</p

Personal semantics: Is it distinct from episodic and semantic memory? An electrophysiological study of memory for autobiographical facts and repeated events in honor of Shlomo Bentin

Declarative memory is thought to consist of two independent systems: episodic and semantic. Episodic memory represents personal and contextually unique events, while semantic memory represents culturally-shared, acontextual factual knowledge. Personal semantics refers to aspects of declarative memory that appear to fall somewhere in between the extremes of episodic and semantic. Examples include autobiographical knowledge and memories of repeated personal events. These two aspects of personal semantics have been studied little and rarely compared to both semantic and episodic memory. We recorded the event-related potentials (ERPs) of 27 healthy participants while they verified the veracity of sentences probing four types of questions: general (i.e., semantic) facts, autobiographical facts, repeated events, and unique (i.e., episodic) events. Behavioral results showed equivalent reaction times in all 4 conditions. True sentences were verified faster than false sentences, except for unique events for which no significant difference was observed. Electrophysiological results showed that the N400 (which is classically associated with retrieval from semantic memory) was maximal for general facts and the LPC (which is classically associated with retrieval from episodic memory) was maximal for unique events. For both ERP components, the two personal semantic conditions (i.e., autobiographical facts and repeated events) systematically differed from semantic memory. In addition, N400 amplitudes also differentiated autobiographical facts from unique events. Autobiographical facts and repeated events did not differ significantly from each other but their corresponding scalp distributions differed from those associated with general facts. Our results suggest that the neural correlates of personal semantics can be distinguished from those of semantic and episodic memory, and may provide clues as to how unique events are transformed to semantic memory

Molecular correlates of host specialization in Staphylococcus aureus

The majority of Staphylococcus aureus isolates that are recovered from either serious infections in humans or from mastitis in cattle represent genetically distinct sets of clonal groups. Moreover, population genetic analyses have provided strong evidence of host specialization among S. aureus clonal groups associated with human and ruminant infection. However, the molecular basis of host specialization in S. aureus is not understood.We sequenced the genome of strain ET3-1, a representative isolate of a common bovine mastitis-causing S. aureus clone. Strain ET3-1 encodes several genomic elements that have not been previously identified in S. aureus, including homologs of virulence factors from other gram-positive pathogens. Relative to the other sequenced S. aureus associated with human infection, allelic variation in ET3-1 was high among virulence and surface-associated genes involved in host colonization, toxin production, iron metabolism, antibiotic resistance, and gene regulation. Interestingly, a number of well-characterized S. aureus virulence factors, including protein A and clumping factor A, exist as pseudogenes in ET3-1. Whole-genome DNA microarray hybridization revealed considerable similarity in the gene content of highly successful S. aureus clones associated with bovine mastitis, but not among those clones that are only infrequently recovered from bovine hosts.Whole genome sequencing and comparative genomic analyses revealed a set of molecular genetic features that distinguish clones of highly successful bovine-associated S. aureus optimized for mastitis pathogenesis in cattle from those that infect human hosts or are only infrequently recovered from bovine sources. Further, the results suggest that modern bovine specialist clones diverged from a common ancestor resembling human-associated S. aureus clones through a combination of foreign DNA acquisition and gene decay