An aging-related cell surface NADH oxidase (arNOX) generates superoxide and is inhibited by coenzyme Q

This report describes a novel ECTO-NOX protein with an oscillating activity having a period length of ca. 26 min encountered with buffy coat fractions and sera of aged individuals (70–100 years) that generates superoxide as measured by the reduction of ferricytochrome c. The oscillating, age-related reduction of ferricytochrome c is sensitive to superoxide dismutase, is inhibited by coenzyme Q and is reduced or absent from sera of younger individuals (20–40 years). An oscillating activity with a regular period length is a defining characteristic of ECTO-NOX proteins (a group of cell surface oxidases with enzymatic activities that oscillate). The period length of ca. 26 min is longer than the period length of 24 min for the usual constitutive (CNOX) ECTO-NOX proteins of the cell surface and sera which neither generate superoxide nor reduce ferricytochrome c. The aging-related ECTO-NOX protein (arNOX) provides a mechanism to transmit cell surface oxidative changes to surrounding cells and circulating lipoproteins potentially important to atherogenesis. Additionally, the findings provide a rational basis for the use of dietary coenzyme Q to retard aging-related arterial lesions.     

Signalling between the hindbrain and paraxial tissues dictates neural crest migration pathways.

Cranial neural crest cells are a pluripotent population of cells derived from the neural tube that migrate into the branchial arches to generate the distinctive bone, connective tissue and peripheral nervous system components characteristic of the vertebrate head. The highly conserved segmental organisation of the vertebrate hindbrain plays an important role in patterning the pathways of neural crest cell migration and in generating the distinct or separate streams of crest cells that form unique structures in each arch. We have used focal injections of DiI into the developing mouse hindbrain in combination with in vitro whole embryo culture to map the patterns of cranial neural crest cell migration into the developing branchial arches. Our results show that mouse hindbrain-derived neural crest cells migrate in three segregated streams adjacent to the even-numbered rhombomeres into the branchial arches, and each stream contains contributions of cells from three rhombomeres in a pattern very similar to that observed in the chick embryo. There are clear neural crest-free zones adjacent to r3 and r5. Furthermore, using grafting and lineage-tracing techniques in cultured mouse embryos to investigate the differential ability of odd and even-numbered segments to generate neural crest cells, we find that odd and even segments have an intrinsic ability to produce equivalent numbers of neural crest cells. This implies that inter-rhombomeric signalling is less important than combinatorial interactions between the hindbrain and the adjacent arch environment in specific regions, in the process of restricting the generation and migration of neural crest cells. This creates crest-free territories and suggests that tissue interactions established during development and patterning of the branchial arches may set up signals that the neural plate is primed to interpret during the progressive events leading to the delamination and migration of neural crest cells. Using interspecies grafting experiments between mouse and chick embryos, we have shown that this process forms part of a conserved mechanism for generating neural crest-free zones and contributing to the separation of migrating crest populations with distinct Hox expression during vertebrate head development.     

Respiratory Phenomics across Multiple Models of Protein Hyperacylation in Cardiac Mitochondria Reveals a Marginal Impact on Bioenergetics

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Adipokines and Obesity Are Associated with Colorectal Polyps in Adult Males: A Cross-Sectional Study

Background

Obesity increases the risk of colon cancer. It is also known that most colorectal cancers develop from adenomatous polyps. However, the effects of obesity and adipokines on colonic polyp formation are unknown.

Methods

To determine if BMI, waist circumference or adipokines are associated with colon polyps in males, 126 asymptomatic men (48–65 yr) were recruited at time of colonoscopy, and anthropometric measures as well as blood were collected. Odds ratios were determined using polytomous logistic regression for polyp number (0 or ≥3) and polyp type (no polyp, hyperplastic polyp, tubular adenoma).

Results

41% of the men in our study were obese (BMI ≥30). The odds of an obese individual having ≥3 polyps was 6.5 (CI: 1.3–33.0) times greater than those of a lean (BMI<25) individual. Additionally, relative to lean individuals, obese individuals were 7.8 (CI: 2.0–30.8) times more likely to have a tubular adenoma than no polyp. As BMI category increased, participants were 2.9 (CI: 1.5–5.4) times more likely to have a tubular adenoma than no polyps. Serum leptin, IP-10 and TNF-α were significantly associated with tubular adenoma presence. Serum leptin and IP-10 were significantly associated with increased likelihood of ≥3 polyps, and TNF-α showed a trend (p = 0.09).

Conclusions

Obese men are more likely to have at least three polyps and adenomas. This cross-sectional study provides evidence that colonoscopy should be recommended for obese, white males.     

Surveillance for peri-elimination trachoma recrudescence: Exploratory studies in Ghana

IntroductionTo date, eleven countries have been validated as having eliminated trachoma as a public health problem, including Ghana in 2018. Surveillance for recrudescence is needed both pre- and post-validation but evidence-based guidance on appropriate strategies is lacking. We explored two potential surveillance strategies in Ghana.Methodology/principal findingsAmongst randomly-selected communities enrolled in pre-validation on-going surveillance between 2011 and 2015, eight were identified as having had trachomatous-inflammation follicular (TF) prevalence ≥5% in children aged 1–9 years between 2012 and 2014. These eight were re-visited in 2015 and 2016 and neighbouring communities were also added (“TF trigger” investigations). Resident children aged 1–9 years were then examined for trachoma and had a conjunctival swab to test for Chlamydia trachomatis (Ct) and a dried blood spot (DBS) taken to test for anti-Pgp3 antibodies. These investigations identified at least one community with evidence of probable recent Ct ocular transmission. However, the approach likely lacks sufficient spatio-temporal power to be reliable.A post-validation surveillance strategy was also evaluated, this reviewed the ocular Ct infection and anti-Pgp3 seroprevalence data from the TF trigger investigations and from the pre-validation surveillance surveys in 2015 and 2016. Three communities identified as having ocular Ct infection >0% and anti-Pgp3 seroprevalence ≥15.0% were identified, and along with three linked communities, were followed-up as part of the surveillance strategy. An additional three communities with a seroprevalence ≥25.0% but no Ct infection were also followed up (“antibody and infection trigger” investigations). DBS were taken from all residents aged ≥1 year and ocular swabs from all children aged 1–9 years. There was evidence of transmission in the group of communities visited in one district (Zabzugu-Tatale). There was no or little evidence of continued transmission in other districts, suggesting previous infection identified was transient or potentially not true ocular Ct infection.Conclusions/significanceThere is evidence of heterogeneity in Ct transmission dynamics in northern Ghana, even 10 years after wide-scale MDA has stopped. There is added value in monitoring Ct infection and anti-Ct antibodies, using these indicators to interrogate past or present surveillance strategies. This can result in a deeper understanding of transmission dynamics and inform new post-validation surveillance strategies. Opportunities should be explored for integrating PCR and serological-based markers into surveys conducted in trachoma elimination settings.     

Restoration of cutaneous pigmentation by transplantation to mice of isogeneic human melanocytes in dermal–epidermal engineered skin substitutes

Autologous engineered skin substitutes (ESS) containing melanocytes (hM) may restore pigmentation and photoprotection after grafting to full‐thickness skin wounds. In this study, normal hM were isolated from discard skin, propagated with or without tyrosinase inhibitors, cryopreserved, recovered into culture, and added to ESS (ESS‐P) before transplantation. ESS‐P were incubated in either UCMC160/161 or UCDM1 medium, scored for hM densities, and grafted to mice. The results showed that sufficient hM can be propagated to expand donor tissue by 100‐fold; incubation of hM in tyrosinase inhibitors reduced pigment levels but did not change hM recovery after cryopreservation; hM densities in ESS‐P were greater after incubation in UCDM1 than UCMC160 medium; hM were localized to the dermal–epidermal junction of ESS‐P; and UCDM1 medium promoted earlier pigment distribution and density. These results indicate that hM can be incorporated into ESS‐P efficiently to restore cutaneous pigmentation and UV photoprotection after full‐thickness skin loss conditions.     

Fisheries management in practice: review of 13 commercially important fish stocks

This paper comparatively reviews several commercially important fish stocks, their state and their management in various regions of the world including Japanese anchovy, Bay of Biscay anchovy, North Sea sandeel, North Sea herring, Icelandic cod, Barents Sea cod, South African cape hakes, sockeye salmon, chinook salmon, southern bluefin tuna, Pacific halibut, Greenland halibut and Patagonian toothfish. The reviewed fish stocks are systemized in three categories: (1) stock properties and status; (2) management structure and objectives; and (3) management advice. We gather evidence to outline qualities of management regimes that are recommended and highlight those that most often fail. Robust management, biological limits (reference points), implementation and consensus are critical points that separate successful and unsuccessful management regimes. We evaluate each fish stock’s management performance relative to its management objectives and current conservation issues. Furthermore, we point out the importance of stakeholder involvement in fisheries management as well as the problems that international fisheries commissions face through examples from the case studies. Management successes tended to be single-nation and single-stock fisheries with capacity control and clear stakeholder involvement. Fisheries with fleet overcapacity, unclear objectives and illegal activity characterized the case studies with management problems.