Understanding the apparent fractional charge of protons in the aqueous electrochemical double layer

A detailed atomic-scale description of the electrochemical interface is essential to the understanding of electrochemical energy transformations. In this work, we investigate the charge of solvated protons at the Pt(111) | H_2O and Al(111) | H_2O interfaces. Using semi-local density-functional theory as well as hybrid functionals and embedded correlated wavefunction methods as higher-level benchmarks, we show that the effective charge of a solvated proton in the electrochemical double layer or outer Helmholtz plane at all levels of theory is fractional, when the solvated proton and solvent band edges are aligned correctly with the Fermi level of the metal (E_F). The observed fractional charge in the absence of frontier band misalignment arises from a significant overlap between the proton and the electron density from the metal surface, and results in an energetic difference between protons in bulk solution and those in the outer Helmholtz plane

Revised timeline and distribution of the earliest diverged human maternal lineages in southern Africa

The oldest extant human maternal lineages include mitochondrial haplogroups L0d and L0k found in the southern African click-speaking forager peoples broadly classified as Khoesan. Profiling these early mitochondrial lineages allows for better understanding of modern human evolution. In this study, we profile 77 new early-diverged complete mitochondrial genomes and sub-classify another 105 L0d/L0k individuals from southern Africa. We use this data to refine basal phylogenetic divergence, coalescence times and Khoesan prehistory. Our results confirm L0d as the earliest diverged lineage (∼172 kya, 95%CI: 149-199 kya), followed by L0k (∼159 kya, 95%CI: 136-183 kya) and a new lineage we name L0g (∼94 kya, 95%CI: 72-116 kya). We identify two new L0d1 subclades we name L0d1d and L0d1c4/L0d1e, and estimate L0d2 and L0d1 divergence at ∼93 kya (95%CI:76-112 kya). We concur the earliest emerging L0d1’2 sublineage L0d1b (∼49 kya, 95%CI:37-58 kya) is widely distributed across southern Africa. Concomitantly, we find the most recent sublineage L0d2a (∼17 kya, 95%CI:10-27 kya) to be equally common. While we agree that lineages L0d1c and L0k1a are restricted to contemporary inland Khoesan populations, our observed predominance of L0d2a and L0d1a in non-Khoesan populations suggests a once independent coastal Khoesan prehistory. The distribution of early-diverged human maternal lineages within contemporary southern Africans suggests a rich history of human existence prior to any archaeological evidence of migration into the region. For the first time, we provide a genetic-based evidence for significant modern human evolution in southern Africa at the time of the Last Glacial Maximum at between ∼21-17 kya, coinciding with the emergence of major lineages L0d1a, L0d2b, L0d2d and L0d2a

Asia Oceania Guidelines for the Implementation of Programs for Cervical Cancer Prevention and Control

This paper aims to provide evidence-based recommendations for health professionals, to develop a comprehensive cervical cancer program for a clinic, a community, or a country. Ensuring access to healthcare is the responsibility of all societies, and the Asia Oceania Research Organisation in Genital Infections and Neoplasia (AOGIN) is committed to working collaboratively with governments and health professionals to facilitate prevention programs, to protect girls and women from cervical cancer, a disease that globally affects 500,000 and kills nearly 300,000 women annually, just over half of whom are in the Asia Oceania region. We share the vision that a comprehensive program of vaccination, screening, and treatment should be made accessible to all girls and women in the world. The primary purpose of these guidelines is to provide information on scientific evidence on the different modalities and approaches of cervical cancer prevention programs, for high resource and low resource settings. The secondary purpose is to provide an overview of the current situation of cervical cancer control and prevention in various Asian Oceania countries: their views of an ideal program, identified obstacles, and suggestions to overcome them are discussed

Physical Activity and Survival After Prostate Cancer

AbstractBackgroundDespite the high global prevalence of prostate cancer (PCa), few epidemiologic studies have assessed physical activity in relation to PCa survival.ObjectiveTo evaluate different types, intensities, and timing of physical activity relative to PCa survival.Design, setting, and participantsA prospective study was conducted in Alberta, Canada, in a cohort of 830 stage II–IV incident PCa cases diagnosed between 1997 and 2000 with follow-up to 2014 (up to 17 yr). Prediagnosis lifetime activity was self-reported at diagnosis. Postdiagnosis activity was self-reported up to three times during follow-up.Outcome measurements and statistical analysisCox proportional hazards models related physical activity to all-cause and PCa-specific deaths and to first recurrence/progression of PCa.Results and limitationsA total of 458 deaths, 170 PCa-specific deaths, and, after first follow-up, 239 first recurrences/progressions occurred. Postdiagnosis total activity (>119 vs ≤42 metabolic equivalent [MET]-hours/week per year) was associated with a significantly lower all-cause mortality risk (hazard ratio [HR]: 0.58; 95% confidence interval [CI], 0.42–0.79; p value for trend <0.01). Postdiagnosis recreational activity (>26 vs ≤4 MET-hours/week per year) was associated with a significantly lower PCa-specific mortality risk (HR: 0.56; 95% CI, 0.35–0.90; p value for trend = 0.01). Sustained recreational activity before and after diagnosis (>18–20 vs <7–8 MET-hours/week per year) was associated with a lower risk of all-cause mortality (HR: 0.66; 95% CI, 0.49–0.88). Limitations included generalisability to healthier cases and an observational study design.ConclusionsThese findings support emerging recommendations to increase physical activity after the diagnosis of PCa and would inform a future exercise intervention trial examining PCa outcomes.Patient summaryIn a 17-yr prostate cancer (PCa) survival study, men who survived at least 2 yr who were more physically active postdiagnosis or performed more recreational physical activity before and after diagnosis survived longer. Recreational physical activity after diagnosis was associated with a lower risk of PCa death

Quantitative High-Speed Laryngoscopic Analysis of Vocal Fold Vibration in Fatigued Voice of Young Karaoke Singers

Summary: Purpose. The present study aimed to determine whether there were physiological differences in the vocal fold vibration between nonfatigued and fatigued voices using high-speed laryngoscopic imaging and quantitative analysis. Methods. Twenty participants aged from 18 to 23 years (mean, 21.2 years; standard deviation, 1.3 years) with normal voice were recruited to participate in an extended singing task. Vocal fatigue was induced using a singing task. Highspeed laryngoscopic image recordings of /i/ phonation were taken before and after the singing task. The laryngoscopic images were semiautomatically analyzed with the quantitative high-speed video processing program to extract indices related to the anteroposterior dimension (length), transverse dimension (width), and the speed of opening and closing. Results. Significant reduction in the glottal length-to-width ratio index was found after vocal fatigue. Physiologically, this indicated either a significantly shorter (anteroposteriorly) or a wider (transversely) glottis after vocal fatigue. Conclusion. The high-speed imaging technique using quantitative analysis has the potential for early identification of vocally fatigued voice

The compression type of coronary artery motion in patients with ST-segment elevation acute myocardial infarction and normal controls: a case-control study

<p>Abstract</p> <p>Background</p> <p>Prediction of the location of culprit lesions responsible for ST-segment elevation myocardial infarctions may allow for prevention of these events. A retrospective analysis of coronary artery motion (CAM) was performed on coronary angiograms of 20 patients who subsequently had ST-segment elevation myocardial infarction treated by primary or rescue angioplasty and an equal number of age and sex matched controls with normal angiograms.</p> <p>Findings</p> <p>There was no statistically significant difference between the frequency of CAM types of the ST-segment elevation acute myocardial infarction and control patients (p = 0.97). The compression type of CAM is more frequent in the proximal and mid segments of all three coronary arteries. No statistically significant difference was found when the frequency of the compression type of CAM was compared between the ST-segment elevation acute myocardial infarction and control patients for the individual coronary artery segments (p = 0.59).</p> <p>Conclusion</p> <p>The proportion of the compression type of coronary artery motion for individual artery segments is not different between patients who have subsequent ST-segment elevation myocardial infarctions and normal controls.</p

RASSF1A–LATS1 signalling stabilizes replication forks by restricting CDK2-mediated phosphorylation of BRCA2

Genomic instability is a key hallmark of cancer leading to tumour heterogeneity and therapeutic resistance. ​BRCA2 has a fundamental role in error-free DNA repair but also sustains genome integrity by promoting ​RAD51 nucleofilament formation at stalled replication forks. ​CDK2 phosphorylates ​BRCA2 (pS3291-​BRCA2) to limit stabilizing contacts with polymerized ​RAD51; however, how replication stress modulates ​CDK2 activity and whether loss of pS3291-​BRCA2 regulation results in genomic instability of tumours are not known. Here we demonstrate that the Hippo pathway kinase ​LATS1 interacts with ​CDK2 in response to genotoxic stress to constrain pS3291-​BRCA2 and support ​RAD51 nucleofilaments, thereby maintaining genomic fidelity during replication stalling. We also show that ​LATS1 forms part of an ​ATR-mediated response to replication stress that requires the tumour suppressor ​RASSF1A. Importantly, perturbation of the ​ATR–​RASSF1A–​LATS1 signalling axis leads to genomic defects associated with loss of ​BRCA2 function and contributes to genomic instability and ‘BRCA-ness’ in lung cancers

Targeting of Slc25a21 is associated with orofacial defects and otitis media due to disrupted expression of a neighbouring gene.

Homozygosity for Slc25a21(tm1a(KOMP)Wtsi) results in mice exhibiting orofacial abnormalities, alterations in carpal and rugae structures, hearing impairment and inflammation in the middle ear. In humans it has been hypothesised that the 2-oxoadipate mitochondrial carrier coded by SLC25A21 may be involved in the disease 2-oxoadipate acidaemia. Unexpectedly, no 2-oxoadipate acidaemia-like symptoms were observed in animals homozygous for Slc25a21(tm1a(KOMP)Wtsi) despite confirmation that this allele reduces Slc25a21 expression by 71.3%. To study the complete knockout, an allelic series was generated using the loxP and FRT sites typical of a Knockout Mouse Project allele. After removal of the critical exon and neomycin selection cassette, Slc25a21 knockout mice homozygous for the Slc25a21(tm1b(KOMP)Wtsi) and Slc25a21(tm1d(KOMP)Wtsi) alleles were phenotypically indistinguishable from wild-type. This led us to explore the genomic environment of Slc25a21 and to discover that expression of Pax9, located 3' of the target gene, was reduced in homozygous Slc25a21(tm1a(KOMP)Wtsi) mice. We hypothesize that the presence of the selection cassette is the cause of the down regulation of Pax9 observed. The phenotypes we observed in homozygous Slc25a21(tm1a(KOMP)Wtsi) mice were broadly consistent with a hypomorphic Pax9 allele with the exception of otitis media and hearing impairment which may be a novel consequence of Pax9 down regulation. We explore the ramifications associated with this particular targeted mutation and emphasise the need to interpret phenotypes taking into consideration all potential underlying genetic mechanisms

Understanding the apparent fractional charge of protons in the aqueous electrochemical double layer

A detailed atomic-scale description of the electrochemical interface is essential to the understanding of electrochemical energy transformations. In this work, we investigate the charge of solvated protons at the Pt(111) | H_2O and Al(111) | H_2O interfaces. Using semi-local density-functional theory as well as hybrid functionals and embedded correlated wavefunction methods as higher-level benchmarks, we show that the effective charge of a solvated proton in the electrochemical double layer or outer Helmholtz plane at all levels of theory is fractional, when the solvated proton and solvent band edges are aligned correctly with the Fermi level of the metal (E_F). The observed fractional charge in the absence of frontier band misalignment arises from a significant overlap between the proton and the electron density from the metal surface, and results in an energetic difference between protons in bulk solution and those in the outer Helmholtz plane