Whole-Genome Sequencing of the World’s Oldest People

Supercentenarians (110 years or older) are the world’s oldest people. Seventy four are alive worldwide, with twenty two in the United States. We performed whole-genome sequencing on 17 supercentenarians to explore the genetic basis underlying extreme human longevity. We found no significant evidence of enrichment for a single rare protein-altering variant or for a gene harboring different rare protein altering variants in supercentenarian compared to control genomes. We followed up on the gene most enriched for rare protein-altering variants in our cohort of supercentenarians, TSHZ3, by sequencing it in a second cohort of 99 long-lived individuals but did not find a significant enrichment. The genome of one supercentenarian had a pathogenic mutation in DSC2, known to predispose to arrhythmogenic right ventricular cardiomyopathy, which is recommended to be reported to this individual as an incidental finding according to a recent position statement by the American College of Medical Genetics and Genomics. Even with this pathogenic mutation, the proband lived to over 110 years. The entire list of rare protein-altering variants and DNA sequence of all 17 supercentenarian genomes is available as a resource to assist the discovery of the genetic basis of extreme longevity in future studies.     

Phytotaxonomy in the People’s Republic of China

As three of the members of the delegation of the Botanical Society of America, the authors participated in a 28-day tour of the People’s Republic of China in May and June, 1978. Botanical institutes and universities were visited in nine cities. A list of names and addresses of the collaborators and editors of family treatments for theFlora Reipublicae Popularis Sinicae is supplemented with a bibliography of published floras and significant taxonomic literature issued primarily since the end of the Cultural Revolution. A few observations on herbaria and herbarium practices are included.     

Asymptotic Behavior of Eigen’s Quasispecies Model

We study Eigen’s quasispecies model in the asymptotic regime where the length of the genotypes goes to \(\infty \) and the mutation probability goes to 0. A limiting infinite system of differential equations is obtained. We prove convergence of trajectories, as well as convergence of the equilibrium solutions. We give analogous results for a discrete-time version of Eigen’s model, which coincides with a model proposed by Moran.     

Flexibility of the N-Terminal mVDAC1 Segment Controls the Channel’s Gating Behavior

Since the solution of the molecular structures of members of the voltage dependent anion channels (VDACs), the N-terminal α-helix has been the main focus of attention, since its strategic location, in combination with its putative conformational flexibility, could define or control the channel’s gating characteristics. Through engineering of two double-cysteine mVDAC1 variants we achieved fixing of the N-terminal segment at the bottom and midpoint of the pore. Whilst cross-linking at the midpoint resulted in the channel remaining constitutively open, cross-linking at the base resulted in an “asymmetric” gating behavior, with closure only at one electric field´s orientation depending on the channel’s orientation in the lipid bilayer. Additionally, and while the native channel adopts several well-defined closed states (S1 and S2), the cross-linked variants showed upon closure a clear preference for the S2 state. With native-channel characteristics restored following reduction of the cysteines, it is evident that the conformational flexibility of the N-terminal segment plays indeed a major part in the control of the channel’s gating behavior.     

Michurinist Biology in the People’s Republic of China, 1948–1956

Michurinist biology was introduced to China in 1948; granted a state supported monopoly in 1952; and reduced to parity with western genetics from 1956. The Soviets exported it through the propaganda agencies Sino Soviet Friendship Association (SSFA) and VOKS (Cultural Relations with Foreign Countries). China’s Ministry of Agriculture achieved broad public awareness and acceptance of Michurinist biology through a translation, publication, and Soviet guest speakers campaign – all managed by a team of agriculturalists led by Luo Tianyu, a veteran CCP (Communist Party) cadre. The campaign grew exponentially, but did not affect university or Chinese Academy of Sciences biology. Luo Tianyu’s failed attempt to force Michurinist biology on a Beijing university triggered its second stage: monopoly status and a ban on “Mendelist-Morganist” biology in teaching, research, and publication. The CCP Central Committee supported this policy believing that Michurinst biology would increase agricultural production for the forthcoming first Five Year Plan; whereas, western genetics had no practical value. Michurinist biology flourished at all levels of education, research, and science literature; Western genetics was completely shut down. This only began to change when the CCP Central Committee became wary of China’s dependency on Soviet technical expertise and failure to fully utilize that of China. Change was further promoted by significant attacks on Michurinist biology by Soviet and East German biologists. Soon, these developments informed China’s “genetics question,” which became a test case for larger questions about the definition of science and the relationship between scientists and the state. Under the guidance of Lu Dingyi’s Central Committee Propaganda Department, the CCP eventually decided that, henceforth, science controversies would only be resolved by the science community; and that monopolies or ideological orthodoxies would not be imposed on science. At the same time, the CCP rescinded Michurinist biology’s monopoly and the ban on western genetics. By the mid-1960s western genetics had successfully restored itself, largely due to the leadership of C. C. Tan, a former student of Dobzhansky. Michurinist biology’s presence shrank and it became marginalized.     

Determination of the Bimetallic Layers’ Film Thicknesses by Phase Detection of SPR Prism Coupler

Plasmonics - In this paper, the phase detection method is demonstrated to determine the film thicknesses of bimetallic layers by surface plasmon resonance (SPR) prism coupler. It was proposed and...     

Do People Use the Shortest Path? An Empirical Test of Wardrop’s First Principle

Most recent route choice models, following either the random utility maximization or rule-based paradigm, require explicit enumeration of feasible routes. The quality of model estimation and prediction is sensitive to the appropriateness of the consideration set. However, few empirical studies of revealed route characteristics have been reported in the literature. This study evaluates the widely applied shortest path assumption by evaluating routes followed by residents of the Minneapolis—St. Paul metropolitan area. Accurate Global Positioning System (GPS) and Geographic Information System (GIS) data were employed to reveal routes people used over an eight to thirteen week period. Most people did not choose the shortest path. Using three weeks of that data, we find that current route choice set generation algorithms do not reveal the majority of paths that individuals took. Findings from this study may guide future efforts in building better route choice models.     

Disparity estimation through Green’s functions of matching equations

Binocular disparities arise from positional differences of scene features projected in the two retinae, and constitute the primary sensory cue for stereo vision. Here we introduce a new computational model for disparity estimation, based on the Green’s function of an image matching equation. When filtering a Gabor-function-modulated signal, the considered Green’s function yields a similarly modulated but shifted version of the original signal. Since a Gabor function models the receptive field of a cortical simple cell, the Green’s kernel thus allows the simulation of relative shifts between the cell’s left and right binocular inputs. A measure of the local degree of matching of such shifted inputs can then be introduced which affords disparity estimation in a similar manner to the energy model of the complex cortical cells. We have therefore effectively reformulated, in physiologically plausible terms, an image matching approach to disparity estimation. Our experiments show that the Green’s function method allows the detection of disparities both from random-dot and real-world stereograms. Partially supported by CNPq-Brazil.     

Re-Examining of Moffitt’s Theory of Delinquency through Agent Based Modeling

Moffitt’s theory of delinquency suggests that at-risk youths can be divided into two groups, the adolescence- limited group and the life-course-persistent group, predetermined at a young age, and social interactions between these two groups become important during the adolescent years. We built an agent-based model based on the microscopic interactions Moffitt described: (i) a maturity gap that dictates (ii) the cost and reward of antisocial behavior, and (iii) agents imitating the antisocial behaviors of others more successful than themselves, to find indeed the two groups emerging in our simulations. Moreover, through an intervention simulation where we moved selected agents from one social network to another, we also found that the social network plays an important role in shaping the life course outcome.     

Evidence for Mate Guarding Behavior in the Taylor’s Checkerspot Butterfly

Discerning the intricacies of mating systems in butterflies can be difficult, particularly when multiple mating strategies are employed and are cryptic and not exclusive. We observed the behavior and habitat use of 113 male Taylor’s checkerspot butterflies (Euphydryas editha taylori). We confirmed that two distinct mating strategies were exhibited; patrolling and perching. These strategies varied temporally in relation to the protandrous mating system employed. Among perching males, we recorded high site fidelity and aggressive defense of small (<5 m²) territories. This territoriality was not clearly a function of classic or non-classic resource defense (i.e., host plants or landscape), but rather appeared to constitute guarding of female pupae (virgin females). This discrete behavior is previously undocumented for this species and has rarely been observed in butterflies.     

Family Income Affects Children’s Altruistic Behavior in the Dictator Game

This study aimed to examine how family income and social distance influence young rural Chinese children’s altruistic behavior in the dictator game (DG). A total of 469 four-year-old children from eight rural areas in China, including many children left behind by parents who had migrated to urban areas for work, played the DG. Stickers comprised the resource, while recipients in the game were assumed to be either their friends or strangers, with the social distance (i.e., strangers compared to friends) as a between-subjects variable. Children donated significantly more stickers to their friends than to strangers. Moreover, children from lower income families donated more stickers than children from higher income families. However, no gender and parental migrant status differences in children’s prosocial behaviors were evident in this sample. Findings of this study suggest that children’s altruistic behaviours to peers are influenced by family characteristics since preschool age. The probable influence of local socialization practices on development and the possible adaptive significance were discussed.     

Interpreting People’s Behavior Toward Primates Using Qualitative Data: a Case Study from North Morocco

International Journal of Primatology - People’s perceptions of primates vary across and within cultures and may not be consistent with their behavior toward the primates themselves. We used...     

Understanding the genetic and molecular pathogenesis of Friedreich’s ataxia through animal and cellular models

In 1996, a link was identified between Friedreich’s ataxia (FRDA), the most common inherited ataxia in men, and alterations in the gene encoding frataxin (FXN). Initial studies revealed that the disease is caused by a unique, most frequently biallelic, expansion of the GAA sequence in intron 1 of FXN. Since the identification of this link, there has been tremendous progress in understanding frataxin function and the mechanism of FRDA pathology, as well as in developing diagnostics and therapeutic approaches for the disease. These advances were the subject of the 4th International Friedreich’s Ataxia Conference held on 5th–7th May in the Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France. More than 200 scientists gathered from all over the world to present the results of research spanning all areas of investigation into FRDA (including clinical aspects, FRDA pathogenesis, genetics and epigenetics of the disease, development of new models of FRDA, and drug discovery). This review provides an update on the understanding of frataxin function, developments of animal and cellular models of the disease, and recent advances in trying to uncover potential molecules for therapy.     

Iwao’s patchiness regression through the origin: biological importance and efficiency of sampling applications

Iwao’s mean crowding-mean density relation can be treated both as a linear function describing the biological characteristics of a species at a population level, or a regression model fitted to empirical data (Iwao’s patchiness regression). In this latter form its parameters are commonly used to construct sampling plans for insect pests, which are characteristically patchily distributed or overdispersed. It is shown in this paper that modifying both the linear function and statistical model to force the intercept or lower functional limit through the origin results in more intuitive biological interpretation of parameters and better sampling economy. Firstly, forcing the function through the origin has the effect of ensuring that zero crowding occurs when zero individuals occupy a patch. Secondly, it ensures that negative values of the intercept, which do not yield an intuitive biological interpretation, will not arise. It is shown analytically that sequential sampling plans based on regression through the origin should be more efficient compared to plans based on conventional regression. For two overdispersed data sets, through-origin based plans collected a significantly lower sample size during validation than plans based on conventional regression, but the improvement in sampling efficiency was not large enough to be of practical benefit. No difference in sample size was observed when through-origin and conventional regression based plans were validated using underdispersed data. A field researcher wishing to adopt a through-origin form of Iwao’s regression for the biological reasons outlined above can therefore be confident that their sampling strategies will not be affected by doing so.     

Predicting the Outcome of Sjogren’s Syndrome-Associated Non-Hodgkin’s Lymphoma Patients

BackgroundNon-Hodgkin''s lymphoma (NHL) development in Sjögren’s syndrome (SS) remains a potentially lethal complication and efforts should focus on the identification of predictors that could aid in appropriate therapeutic decisions.MethodsIn order to identify potential prognostic factors for outcome in SS-associated NHL, we retrospectively analyzed a cohort of 77 patients, diagnosed with NHL according to WHO classification criteria and meeting the American-European Consensus Classification (AECC) criteria for SS and examined the effect of SS-activity (defined as the EULAR SS disease activity index-ESSDAI) in the prognosis of SS-related NHLs, as defined in terms of overall and event-free survivals (OS and EFS). An event was defined as lymphoma relapse, treatment failure, disease progression, histological transformation or death. The effect of NHL clinical and laboratory characteristics was also investigated.ResultsMALT lymphomas constituted the majority (66.2%) of lymphomas. During the follow-up (median = 57.93 months), the 5-year OS was 90.91% (95% CI: 82.14–95.80%) and the EFS was 77.92% (95% CI: 67.37–85.82%). Patients with high ESSDAI score at lymphoma diagnosis had a greater risk for death (OR = 5.241, 95% CI: 1.034–26.568) or for event (OR = 4.317, 95% CI: 1.146–9.699, p = 0.008). These patients had also significantly worse EFS (HR = 4.541, 95% CI: 1.772–11.637) and OS (HR = 5.946, 95% CI: 1.259–28.077). In addition, post-chemotherapy ESSDAI improvement was significantly lower in patients who had experienced an event (p = 0.005). An unfavorable International prognostic index (IPI) score (high-intermediate/high) was associated with high risk of death and event (OR = 13.867, 95% CI: 2.656–72.387 and OR = 12.589, 95% CI: 3.911–40.526, respectively), worse EFS (log-rank p<0.001, HR = 8.718, 95% CI: 3.477–21.858), as well as with worse OS (log-rank p<0.001, HR = 11.414, 95% CI: 2.414–53.974). After adjustment for identified risk factors, IPI score retained a significant prognostic role following by a strong effect of ESSDAI in survival outcomes.ConclusionsAt the point of NHL diagnosis, IPI and ESSDAI might be proved useful predictive tools in SS-associated lymphoma prognosis, directing to a more patient-tailored approach.     

Experimental Infection of Danish Landrace/Yorkshire Crossbred Pigs with Schistosoma japonicum from the People’s Republic of China

This study was undertaken to assess the suitability of Danish Landrace/Yorkshire (L/Y) crossbred pigs as experimental hosts of a Chinese mainland strain of Schistosoma japonicum. Pigs were exposed to 200, 500 or 1000 cercariae and parasite burdens were determined by perfusion after either 8 or 11 weeks. All pigs became infected with onset of faecal egg excretion 6 to 7 weeks following exposure to cercariae. The pattern of faecal egg excretion differed markedly among the individual animals. Gross hepatic pathological lesions of varying degrees were noted in all of the pigs. Schistosome worm recoveries ranged from 1.5–23.4% of the cercarial exposure dose. Most schistosome eggs recovered from the tissues, expressed as eggs/g tissue, were found in the rectum (91%), caecum (3.1%) and liver (5.1%). The results show that Danish L/Y pigs may serve as appropriate experimental final hosts of the Chinese mainland strain of S. japonicum.     

Effects of Textured Insoles on Balance in People with Parkinson’s Disease

Background

Degradation of the somatosensory system has been implicated in postural instability and increased falls risk for older people and Parkinson’s disease (PD) patients. Here we demonstrate that textured insoles provide a passive intervention that is an inexpensive and accessible means to enhance the somatosensory input from the plantar surface of the feet.

Methods

20 healthy older adults (controls) and 20 participants with PD were recruited for the study. We evaluated effects of manipulating somatosensory information from the plantar surface of the feet using textured insoles. Participants performed standing tests, on two different surfaces (firm and foam), under three footwear conditions: 1) barefoot; 2) smooth insoles; and 3) textured insoles. Standing balance was evaluated using a force plate yielding data on the range of anterior-posterior and medial-lateral sway, as well as standard deviations for anterior-posterior and medial-lateral sway.

Results

On the firm surface with eyes open both the smooth and textured insoles reduced medial-lateral sway in the PD group to a similar level as the controls. Only the textured insole decreased medial-lateral sway and medial-lateral sway standard deviation in the PD group on both surfaces, with and without visual input. Greatest benefits were observed in the PD group while wearing the textured insoles, and when standing on the foam surface with eyes closed.

Conclusions

Data suggested that textured insoles may provide a low-cost means of improving postural stability in high falls-risk groups, such as people with PD.