The structural organization and protein composition of lens fiber junctions.

The structural organization and protein composition of lens fiber junctions isolated from adult bovine and calf lenses were studied using combined electron microscopy, immunolocalization with monoclonal and polyclonal anti-MIP and anti-MP70 (two putative gap junction-forming proteins), and freeze-fracture and label-fracture methods. The major intrinsic protein of lens plasma membranes (MIP) was localized in single membranes and in an extensive network of junctions having flat and undulating surface topologies. In wavy junctions, polyclonal and monoclonal anti-MIPs labeled only the cytoplasmic surface of the convex membrane of the junction. Label-fracture experiments demonstrated that the convex membrane contained MIP arranged in tetragonal arrays 6-7 nm in unit cell dimension. The apposing concave membrane of the junction displayed fracture faces without intramembrane particles or pits. Therefore, wavy junctions are asymmetric structures composed of MIP crystals abutted against particle-free membranes. In thin junctions, anti-MIP labeled the cytoplasmic surfaces of both apposing membranes with varying degrees of asymmetry. In thin junctions, MIP was found organized in both small clusters and single membranes. These small clusters also abut against particle-free apposing membranes, probably in a staggered or checkerboard pattern. Thus, the structure of thin and wavy junctions differed only in the extent of crystallization of MIP, a property that can explain why this protein can produce two different antibody-labeling patterns. A conclusion of this study is that wavy and thin junctions do not contain coaxially aligned channels, and, in these junctions, MIP is unlikely to form gap junction-like channels. We suggest MIP may behave as an intercellular adhesion protein which can also act as a volume-regulating channel to collapse the lens extracellular space. Junctions constructed of MP70 have a wider overall thickness (18-20 nm) and are abundant in the cortical regions of the lens. A monoclonal antibody raised against this protein labeled these thicker junctions on the cytoplasmic surfaces of both apposing membranes. Thick junctions also contained isolated clusters of MIP inside the plaques of MP70. The role of thick junctions in lens physiology remains to be determined

Towards an early warning system for Rhodesian sleeping sickness in savannah areas: man-like traps for tsetse flies

Background: In the savannahs of East and Southern Africa, tsetse flies (Glossina spp.) transmit Trypanosoma brucei rhodesiense which causes Rhodesian sleeping sickness, the zoonotic form of human African trypanosomiasis. The flies feed mainly on wild and domestic animals and are usually repelled by humans. However, this innate aversion to humans can be undermined by environmental stresses on tsetse populations, so increasing disease risk. To monitor changes in risk, we need traps designed specifically to quantify the responsiveness of savannah tsetse to humans, but the traps currently available are designed to simulate other hosts. Methodology/Principal Findings: In Zimbabwe, two approaches were made towards developing a man-like trap for savannah tsetse: either modifying an ox-like trap or creating new designs. Tsetse catches from a standard ox-like trap used with and without artificial ox odor were reduced by two men standing nearby, by an average of 34% for Glossina morsitans morsitans and 56% for G. pallidipes, thus giving catches more like those made by hand-nets from men. Sampling by electrocuting devices suggested that the men stopped flies arriving near the trap and discouraged trap-entering responses. Most of human repellence was olfactory, as evidenced by the reduction in catches when the trap was used with the odor of hidden men. Geranyl acetone, known to occur in human odor, and dispensed at 0.2 mg/h, was about as repellent as human odor but not as powerfully repellent as wood smoke. New traps looking and smelling like men gave catches like those from men. Conclusion/Significance: Catches from the completely new man-like traps seem too small to give reliable indices of human repellence. Better indications would be provided by comparing the catches of an ox-like trap either with or without artificial human odor. The chemistry and practical applications of the repellence of human odor and smoke deserve further study

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

The early life gut microbiota plays a crucial role in regulating and maintaining the intestinal barrier, with disturbances in these communities linked to dysregulated renewal and replenishment of intestinal epithelial cells. Here we sought to determine pathological cell shedding outcomes throughout the postnatal developmental period, and which host and microbial factors mediate these responses. Surprisingly, neonatal mice (Day 14 and 21) were highly refractory to induction of cell shedding after intraperitoneal administration of liposaccharide (LPS), with Day 29 mice showing strong pathological responses, more similar to those observed in adult mice. These differential responses were not linked to defects in the cellular mechanisms and pathways known to regulate cell shedding responses. When we profiled microbiota and metabolites, we observed significant alterations. Neonatal mice had high relative abundances of Streptococcus, Escherichia, and Enterococcus and increased primary bile acids. In contrast, older mice were dominated by Candidatus Arthromitus, Alistipes, and Lachnoclostridium, and had increased concentrations of SCFAs and methyamines. Antibiotic treatment of neonates restored LPS-induced small intestinal cell shedding, whereas adult fecal microbiota transplant alone had no effect. Our findings further support the importance of the early life window for microbiota-epithelial interactions in the presence of inflammatory stimuli and highlights areas for further investigation

The physiological bases of hidden noise-induced hearing loss: protocol for a functional neuroimaging study

Background: Rodent studies indicate that noise exposure can cause permanent damage to synapses between inner hair cells and high-threshold auditory nerve fibers, without permanently altering threshold sensitivity. These demonstrations of what is commonly known as “hidden hearing loss” have been confirmed in several rodent species, but the implications for human hearing are unclear. Objective: Our Medical Research Council (MRC) funded programme aims to address this unanswered question, by investigating functional consequences of the damage to the human peripheral and central auditory nervous system that results from cumulative lifetime noise exposure. Behavioral and neuroimaging techniques are being used in a series of parallel studies aimed at detecting hidden hearing loss in humans. The planned neuroimaging study aims to (1) identify central auditory biomarkers associated with hidden hearing loss, (2) investigate if there are any additive contributions from tinnitus or diminished sound tolerance, which are often comorbid with hearing problems, and (3) explore the relation between subcortical functional Magnetic Resonance Imaging (fMRI) measures and the auditory brainstem response (ABR). Methods: Individuals aged 25 to 40 years with pure tone hearing thresholds ≤ 20 dB HL over the range 500 Hz to 8 kHz and no contraindications for MRI or signs of ear disease will be recruited into the study. Lifetime noise exposure will be estimated using an in-depth structured interview. Auditory responses throughout the central auditory system will be recorded using ABR and fMRI. Analyses will focus predominantly on correlations between lifetime noise exposure and auditory response characteristics. Results: This article reports the study protocol. The programme grant was awarded in July 2013. Enrollment for the study described in this protocol commenced in February 2017 and was completed in December 2017. Results are expected in 2018. Conclusions: This challenging and comprehensive study will have the potential to impact diagnostic procedures for hidden hearing loss, enabling early identification of noise-induced auditory damage via the detection of changes in central auditory processing. Consequently, this will generate the opportunity to give personalized advice regarding provision of ear defense and monitoring of further damage, thus reducing the incidence of noise-induced hearing loss

Aquatic community response to volcanic eruptions on the Ecuadorian Andean flank: evidence from the palaeoecological record

Aquatic ecosystems in the tropical Andes are under increasing pressure from human modification of the landscape (deforestation and dams) and climatic change (increase of extreme events and 1.5 °C on average temperatures are projected for AD 2100). However, the resilience of these ecosystems to perturbations is poorly understood. Here we use a multi-proxy palaeoecological approach to assess the response of aquatic ecosystems to a major mechanism for natural disturbance, volcanic ash deposition. Specifically, we present data from two Neotropical lakes located on the eastern Andean flank of Ecuador. Laguna Pindo (1°27.132′S–78°04.847′W) is a tectonically formed closed basin surrounded by a dense mid-elevation forest, whereas Laguna Baños (0°19.328′S–78°09.175′W) is a glacially formed lake with an inflow and outflow in high Andean Páramo grasslands. In each lake we examined the dynamics of chironomids and other aquatic and semi-aquatic organisms to explore the effect of thick (> 5 cm) volcanic deposits on the aquatic communities in these two systems with different catchment features. In both lakes past volcanic ash deposition was evident from four large tephras dated to c.850 cal year BP (Pindo), and 4600, 3600 and 1500 cal year BP (Baños). Examination of the chironomid and aquatic assemblages before and after the ash depositions revealed no shift in composition at Pindo, but a major change at Baños occurred after the last event around 1500 cal year BP. Chironomids at Baños changed from an assemblage dominated by Pseudochironomus and Polypedilum nubifer-type to Cricotopus/Paratrichocladius type-II, and such a dominance lasted for approximately 380 years. We suggest that, despite potential changes in the water chemistry, the major effect on the chironomid community resulted from the thickness of the tephra being deposited, which acted to shallow the water body beyond a depth threshold. Changes in the aquatic flora and fauna at the base of the trophic chain can promote cascade effects that may deteriorate the ecosystem, especially when already influenced by human activities, such as deforestation and dams, which is frequent in the high Andes

Identifying people at higher risk of melanoma across the U.K.: a primary-care-based electronic survey

BACKGROUND: Melanoma incidence is rising rapidly worldwide among white populations. Defining higher-risk populations using risk prediction models may help targeted screening and early detection approaches. OBJECTIVES: To assess the feasibility of identifying people at higher risk of melanoma using the Williams self-assessed clinical risk estimation model in U.K. primary care. METHODS: We recruited participants from the waiting rooms of 22 general practices covering a total population of > 240 000 in three U.K. regions: Eastern England, North East Scotland and North Wales. Participants completed an electronic questionnaire using tablet computers. The main outcome was the mean melanoma risk score using the Williams melanoma risk model. RESULTS: Of 9004 people approached, 7742 (86%) completed the electronic questionnaire. The mean melanoma risk score for the 7566 eligible participants was 17·15 ± 8·51, with small regional differences [lower in England compared with Scotland (P = 0·001) and Wales (P < 0·001), mainly due to greater freckling and childhood sunburn among Scottish and Welsh participants]. After weighting to the age and sex distribution, different potential cut-offs would allow between 4% and 20% of the population to be identified as higher risk, and those groups would contain 30% and 60%, respectively of those likely to develop melanoma. CONCLUSIONS: Collecting data on the melanoma risk profile of the general population in U.K. primary care is both feasible and acceptable for patients in a general practice setting, and provides opportunities for new methods of real-time risk assessment and risk stratified cancer interventions

Obesity and diabetes mellitus association in rural community of Katana, South Kivu, in Eastern Democratic Republic of Congo : Bukavu Observ Cohort study results

Background: Factual data exploring the relationship between obesity and diabetes mellitus prevalence from rural areas of sub-Saharan Africa remain scattered and are unreliable. To address this scarceness, this work reports population study data describing the relationship between the obesity and the diabetes mellitus in the general population of the rural area of Katana (South Kivu in the Democratic Republic of the Congo). Methods: A cohort of three thousand, nine hundred, and sixty-two (3962) adults (>15 years old) were followed between 2012 and 2015 (or 4105 person-years during the observation period), and data were collected using the locally adjusted World Health Organization's (WHO) STEPwise approach to Surveillance (STEPS) methodology. The hazard ratio for progression of obesity was calculated. The association between diabetes mellitus and obesity was analyzed with logistic regression. Results: The diabetes mellitus prevalence was 2.8 % versus 3.5 % for obese participants and 7.2 % for those with metabolic syndrome, respectively. Within the diabetes group, 26.9 % had above-normal waist circumference and only 9.8 % were obese. During the median follow-up period of 2 years, the incidence of obesity was 535/100,000 person-years. During the follow-up, the prevalence of abdominal obesity significantly increased by 23 % (p < 0.0001), whereas the increased prevalence of general obesity (7.8 %) was not significant (p = 0.53). Finally, diabetes mellitus was independently associated with age, waist circumference, and blood pressure but not body mass index. Conclusion: This study confirms an association between diabetes mellitus and abdominal obesity but not with general obesity. On the other hand, the rapid increase in abdominal obesity prevalence in this rural area population within the follow-up period calls for the urgent promoting of preventive lifestyle measures

Braided racks, Hurwitz actions and Nichols algebras with many cubic relations

We classify Nichols algebras of irreducible Yetter-Drinfeld modules over groups such that the underlying rack is braided and the homogeneous component of degree three of the Nichols algebra satisfies a given inequality. This assumption turns out to be equivalent to a factorization assumption on the Hilbert series. Besides the known Nichols algebras we obtain a new example. Our method is based on a combinatorial invariant of the Hurwitz orbits with respect to the action of the braid group on three strands.Comment: v2: 35 pages, 6 tables, 14 figure

Accuracy and repeatability of wrist joint angles in boxing using an electromagnetic tracking system

© 2019, The Author(s). The hand-wrist region is reported as the most common injury site in boxing. Boxers are at risk due to the amount of wrist motions when impacting training equipment or their opponents, yet we know relatively little about these motions. This paper describes a new method for quantifying wrist motion in boxing using an electromagnetic tracking system. Surrogate testing procedure utilising a polyamide hand and forearm shape, and in vivo testing procedure utilising 29 elite boxers, were used to assess the accuracy and repeatability of the system. 2D kinematic analysis was used to calculate wrist angles using photogrammetry, whilst the data from the electromagnetic tracking system was processed with visual 3D software. The electromagnetic tracking system agreed with the video-based system (paired t tests) in both the surrogate ( 0.9). In the punch testing, for both repeated jab and hook shots, the electromagnetic tracking system showed good reliability (ICCs > 0.8) and substantial reliability (ICCs > 0.6) for flexion–extension and radial-ulnar deviation angles, respectively. The results indicate that wrist kinematics during punching activities can be measured using an electromagnetic tracking system

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition