Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.

The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible β-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation

Magnetism, FeS colloids, and Origins of Life

A number of features of living systems: reversible interactions and weak bonds underlying motor-dynamics; gel-sol transitions; cellular connected fractal organization; asymmetry in interactions and organization; quantum coherent phenomena; to name some, can have a natural accounting via $physical$ interactions, which we therefore seek to incorporate by expanding the horizons of `chemistry-only' approaches to the origins of life. It is suggested that the magnetic 'face' of the minerals from the inorganic world, recognized to have played a pivotal role in initiating Life, may throw light on some of these issues. A magnetic environment in the form of rocks in the Hadean Ocean could have enabled the accretion and therefore an ordered confinement of super-paramagnetic colloids within a structured phase. A moderate H-field can help magnetic nano-particles to not only overcome thermal fluctuations but also harness them. Such controlled dynamics brings in the possibility of accessing quantum effects, which together with frustrations in magnetic ordering and hysteresis (a natural mechanism for a primitive memory) could throw light on the birth of biological information which, as Abel argues, requires a combination of order and complexity. This scenario gains strength from observations of scale-free framboidal forms of the greigite mineral, with a magnetic basis of assembly. And greigite's metabolic potential plays a key role in the mound scenario of Russell and coworkers-an expansion of which is suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed Krishnaswami Alladi, Springer 201

A systematic review of protocol studies on conceptual design cognition

This paper reports the first systematic review and synthesis of protocol studies on conceptual design cognition. 47 protocol studies from the domains of architectural design, engineering design, and product de-sign engineering were reviewed towards answering the following re-search question: What is our current understanding of the cognitive processes involved in conceptual design tasks carried out by individual designers? Studies were found to reflect three viewpoints on the cognitive nature of designing, namely: design as search; design as ex-ploration; and design activities. Synthesising the findings of individual studies yielded a classification of cognitive processes involved in con-ceptual design tasks, described in different terms across different viewpoints. Towards a common terminology, these processes are posi-tioned within the cognitive psychology literature, revealing seven basic types of process that appear to be fundamental to designing across all viewpoints: memory (working and long term); visual perception; men-tal imagery; attention; semantic association; cognitive control; and higher-order processes, e.g. analysis and reasoning. The development of common cognitive models of conceptual design, grounded in a sci-entifically rigorous understanding of design cognition, is identified as an avenue for future research

Characterising the phenotypic diversity of Papilio dardanus wing patterns using an extensive museum collection

The history of 20th Century evolutionary biology can be followed through the study of mimetic butterflies. From the initial findings of discontinuous polymorphism through the debates regarding the evolution of mimicry and the step-size of evolutionary change, to the studies on supergene evolution and molecular characterisation of butterfly genomes, mimetic butterflies have been at the heart of evolutionary thought for over 100 years. During this time, few species have received as much attention and in-depth study as Papilio dardanus. To assist all aspects of mimicry research, we present a complete data-derived overview of the extent of polymorphism within this species. Using historical samples permanently held by the NHM London, we document the extent of phenotypic variation and characterise the diversity present in each of the subspecies and how it varies across Africa. We also demonstrate an association between “imperfect” mimetic forms and the transitional race formed in the area where Eastern and Western African populations meet around Lake Victoria. We present a novel portal for access to this collection, www.mimeticbutterflies.org, allowing remote access to this unique repository. It is hoped that this online resource can act as a nucleus for the sharing and dissemination of other collections databases and imagery connected with mimetic butterflies

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

First finds of Prunus domestica L. in Italy from the Phoenician and Punic periods (6th-2nd centuries BC)

Abstract During the archaeological excavations in the Phoenician and Punic settlement of Santa Giusta (Oristano, Sardinia, Italy), dating back to the 6th–2nd centuries bc, several Prunus fruitstones (endocarps) inside amphorae were recovered. The exceptional state of preservation of the waterlogged remains allowed morphometric measurements to be done by image analysis and statistical comparisons made with modern cultivated and wild Prunus samples collected in Sardinia. Digital images of modern and archaeological Prunus fruitstones were acquired with a flatbed scanner and analysed by applying image analysis techniques to measure 26 morphometric features. By applying stepwise linear discriminant analysis, a morphometric comparison was made between the archaeological fruitstones of Prunus and the modern ones collected in Sardinia. These analyses allowed identification of 53 archaeological fruitstones as P. spinosa and 11 as P. domestica. Moreover, the archaeological samples of P. spinosa showed morphometric similarities in 92.5% of the cases with the modern P. spinosa samples currently growing near the Phoenician and Punic site. Likewise, the archaeological fruitstones identified as P. domestica showed similarities with the modern variety of P. domestica called Sanguigna di Bosa which is currently cultivated near the village of Bosa. Currently, these findings represent the first evidence of P. domestica in Italy during the Phoenician and Punic periods. Keywords Archaeobotany · Image analysis · Morphometric features · Prunus · Sardini

Etiopathogenic features of acne vulgaris

Acne vulgaris is one of the most frequent dermatoses in the general population. Numerous scientific articles are available on acne, mostly relating to its etiopathogeny. This notwithstanding, the large amount of scientific information generated by works on acne vulgaris has made it difficult to converge knowledge on its etiopathogeny into a single understanding. Therefore, this review has been proposed to analyze the four classic mechanisms of this dermatosis (sebum production, follicular hyperkeratinization, bacterial colonization and glandular inflammation), as well as its secondary mechanism, namely hormonal mediation.A acne vulgar é uma das dermatoses mais freqüentes na população em geral. Encontra-se na literatura grande número de trabalhos científicos referentes sobretudo a sua etiopatogenia. No entanto, dado o grande número de informações geradas a respeito, dificilmente consegue-se reuni-las em entendimento comum. Esta revisão literária foi proposta a fim de abordar os mecanismos etiopatogênicos clássicos da acne vulgar (produção sebácea, hiperqueratinização folicular, colonização bacteriana folicular e inflamação glandular) e o mecanismo coadjuvante principal, a influência hormonal.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Depto. de DermatologiaPontifícia Universidade Católica de Campinas Hospital e Maternidade Celso Pierro Serviço de DermatologiaUNIFESP, EPM, Depto. de DermatologiaSciEL

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Tumours in 177 pet hamsters

Background: Even though tumours are considered to occur frequently in pet hamsters, there is only a small number of scientific reports in current literature. Methods: Pathological reports from 177 hamsters were evaluated. Results: Of these, 78 were male and 75 were female. Median age of affected hamsters was 12 months (range 2–34). Integumental tumours were the most common neoplasms (62%, 109/177). As far as species was known, the number of Syrian hamsters (52%, 30/58) affected by tumours seemed to be lower than the number of affected dwarf hamsters (85%, 47/55). Tumours of the hematopoietic system were the second most frequently neoplasms (17%, 30/177). Relative number of neoplasms of the endocrine system, tumours of the digestive system (1.7%, 3/177) and other tumours (4%, 7/177 each) was low. The majority of integumental tumours were epithelial (66%; 91/126). Conclusion: This study aimed to analyze data from veterinary surgeries and pathological institutes about the occurrence of spontaneous tumours in Syrian hamsters and dwarf hamsters to give information about the frequency of tumours, prognosis and survival time. This is the first study about tumours in pet hamsters in Germany so far

The spectral, spatial and contrast sensitivity of human polarization pattern perception

It is generally believed that humans perceive linear polarized light following its conversion into a luminance signal by diattenuating macular structures. Measures of polarization sensitivity may therefore allow a targeted assessment of macular function. Our aim here was to quantify psychophysical characteristics of human polarization perception using grating and optotype stimuli defined solely by their state of linear polarization. We show: (i) sensitivity to polarization patterns follows the spectral sensitivity of macular pigment; (ii) the change in sensitivity across the central field follows macular pigment density; (iii) polarization patterns are identifiable across a range of contrasts and scales, and can be resolved with an acuity of 15.4 cycles/degree (0.29 logMAR); and (iv) the human eye can discriminate between areas of linear polarization differing in electric field vector orientation by as little as 4.4°. These findings, which support the macular diattenuator model of polarization sensitivity, are unique for vertebrates and approach those of some invertebrates with a well-developed polarization sense. We conclude that this sensory modality extends beyond Haidinger's brushes to the recognition of quantifiable spatial polarization-modulated patterns. Furthermore, the macular origin and sensitivity of human polarization pattern perception makes it potentially suitable for the detection and quantification of macular dysfunction