Colonial green algae in the Cambrian plankton.

The fossil record indicates a major turnover in marine phytoplankton across the Ediacaran-Cambrian transition, coincident with the rise of animal-rich ecosystems. However, the diversity, affinities and ecologies of Cambrian phytoplankton are poorly understood, leaving unclear the role of animal interactions and the drivers of diversification. New exceptionally preserved acritarchs (problematic organic-walled microfossils) from the late early Cambrian (around 510 Ma) reveal colonial organization characterized by rings and plates of interconnected, geometrically arranged cells. The assemblage exhibits a wide but gradational variation in cell size, ornamentation and intercell connection, interpreted as representing one or more species with determinate (coenobial) colony formation via cell division, aggregation and growth by cell expansion. An equivalent strategy is known only among green algae, specifically chlorophycean chlorophytes. The fossils differ in detail from modern freshwater examples and apparently represent an earlier convergent radiation in marine settings. Known trade-offs between sinking risk and predator avoidance in colonial phytoplankton point to adaptations triggered by intensifying grazing pressure during a Cambrian metazoan invasion of the water column. The new fossils reveal that not all small acritarchs are unicellular resting cysts, and support an early Palaeozoic prominence of green algal phytoplankton as predicted by molecular biomarkers.

Ostracods had colonized estuaries by the late Silurian.

The fossil record of terrestrialization documents notable shifts in the environmental and physiological tolerances of many animal and plant groups. However, for certain significant components of modern freshwater and terrestrial environments, the transition out of marine settings remains largely unconstrained. Ostracod crustaceans occupy an exceptional range of modern aquatic environments and are invaluable palaeoenvironmental indicators in the fossil record. However, pre-Carboniferous records of supposed non-marine and marginal marine ostracods are sparse, and the timing of their marine to non-marine transition has proven elusive. Here, we reassess the early environmental history of ostracods in light of new assemblages from the late Silurian of Vietnam. Two, low diversity but distinct ostracod assemblages are associated with estuarine deposits. This occurrence is consistent with previous incidental reports of ostracods occupying marginal and brackish settings through the late Silurian and Devonian. Therefore, ostracods were pioneering the occupation of marginal marine and estuarine settings 60 Myr before the Carboniferous and they were a component of the early phase of transition from marine to non-marine environments.

Pathogen recognition by NK cells amplifies the pro-inflammatory cytokine production of monocyte-derived DC via IFN-γ.

BACKGROUND: Besides their prominent role in the elimination of infected or malignantly transformed cells, natural killer (NK) cells serve as modulators of adaptive immune responses. Enhancing bidirectional crosstalk between NK cells and dendritic cells (DC) is considered a promising tool to potentiate cancer vaccines. We investigated to what extent direct sensing of viral and bacterial motifs by NK cells contributes to the response of inflammatory DC against the same pathogenic stimulus. RESULTS: We demonstrated that sensing of bacterial and viral PAMPs by NK cells contributes to DC cytokine production via NK cell-derived soluble factors. This enhancement of DC cytokine production was dependent on the pattern recognition receptor (PRR) agonist but also on the cytokine environment in which NK cells recognized the pathogen, indicating the importance of accessory cell activation for this mechanism. We showed in blocking experiments that NK cell-mediated amplification of DC cytokine secretion is dependent on NK cell-derived IFN-γ irrespective of the PRR that is sensed by the NK cell. CONCLUSIONS: These findings illustrate the importance of bidirectional interaction between different PRR-expressing immune cells, which can have implications on the selection of adjuvants for vaccination strategies.

Naked chancelloriids from the lower Cambrian of China show evidence for sponge-type growth.

Chancelloriids are an extinct group of spiny Cambrian animals of uncertain phylogenetic position. Despite their sponge-like body plan, their spines are unlike modern sponge spicules, but share several features with the sclerites of certain Cambrian bilaterians, notably halkieriids. However, a proposed homology of these 'coelosclerites' implies complex transitions in body plan evolution. A new species of chancelloriid, Allonnia nuda, from the lower Cambrian (Stage 3) Chengjiang Lagerstätte is distinguished by its large size and sparse spination, with modified apical sclerites surrounding an opening into the body cavity. The sclerite arrangement in A. nuda and certain other chancelloriids indicates that growth involved sclerite addition in a subapical region, thus maintaining distinct zones of body sclerites and apical sclerites. This pattern is not seen in halkieriids, but occurs in some modern calcarean sponges. With scleritome assembly consistent with a sponge affinity, and in the absence of cnidarian- or bilaterian-grade features, it is possible to interpret chancelloriids as sponges with an unusually robust outer epithelium, strict developmental control of body axis formation, distinctive spicule-like structures and, by implication, minute ostia too small to be resolved in fossils. In this light, chancelloriids may contribute to the emerging picture of high disparity among early sponges.

Quality of life in inflammatory neuropathies: the IN-QoL.

BACKGROUND: No consensus exists which quality of life (QoL) measure should be used in patients with inflammatory neuropathies. Moreover, most QoL measures are ordinal-based scales with their known deficiencies. OBJECTIVES: To establish a new disease-specific interval-based QoL questionnaire in inflammatory neuropathies (IN-QoL) using the Rasch model and evaluate its scientific properties (validity, reliability and responsiveness). METHODS: 264 patients with inflammatory neuropathies completed six commonly used QoL questionnaires. The obtained data were stacked and subjected to Rasch analysis. Responsiveness was determined by using the concept of minimum clinically important differences related to varying individually obtained SEs (responsiveness definition: MCID-SE≥1.96 after 1-year follow-up compared with baseline). RESULTS: The IN-QoL fulfilled all Rasch's model requirements with high internal reliability values (patient separation index of 0.94), except being multidimensional. Additional factor analysis resulted in two (functional and mental) subsets that were unidimensional on their own. The IN-QoL showed good correlation with the EuroQol-health quality visual analogue scale (EQ-VAS) (Spearman's rho 0.72). It demonstrated acceptable responsiveness in patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), as did the EQ-VAS. In patients with monoclonal gammopathy-related neuropathy and multifocal motor neuropathy, hardly any changes were seen over time. CONCLUSION: The IN-QoL questionnaire fulfils modern clinimetric requirements and correlates strongly with a patient's self-assessment of their own quality of health, while also showing responsiveness in patients with GBS and CIDP. We propose using the IN-QoL and the EQ-VAS for assessing the QoL of patients with inflammatory neuropathies in future studies.

The development of D antibodies after D-mismatched kidney transplantation in a setting of reduced immunosuppression.

BACKGROUND: D antigens are not taken into account in the allocation of solid organs. Female transplant recipients with D antibodies as a consequence of D-mismatched kidney transplantation may develop hemolytic disease of the fetus and newborn in future pregnancies. We examined D antibody development in transplant recipients who received D-mismatched kidney transplantation in absence of D prophylaxis and in a setting of reduced immunosuppression. STUDY DESIGN AND METHODS: From 1993 until 2015, a total of 1355 kidney patients received transplantations in our center of whom 156 received a D-mismatched graft. A retrospective analysis was conducted; frozen stored sera obtained from transplant recipients 3 months after transplantation were tested for irregular red blood cell (RBC) antibodies using a three-cell screening and an identification panel. In the case of D antibody positivity, additional testing was performed 1 month before transplantation. RESULTS: In seven of 156 (4.5%) transplant recipients we found irregular RBC antibodies after transplantation, of which five (3.2%) were determined to be D antibodies. We observed only one (0.6%) recipient without D antibodies before transplantation. CONCLUSION: Although the risk of D antibody development is considerably lower after D-mismatched kidney transplantation than D-mismatched pregnancy, anti-D prophylaxis may still be advisable for female transplant recipients of childbearing age.

Does ability to walk reflect general functionality in inflammatory neuropathies?

The "ability to walk" is considered a benchmark for good clinical recovery and prognosis, particularly in patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). However, it has never been determined whether being "able to walk" represents general functionality. The purpose of this study was to examine whether the ability to walk outside independently reflects general functional improvement in patients with GBS, CIDP, and gammopathy-related neuropathy (MGUSP). A total of 137 patients with newly diagnosed (or relapsing) GBS (55), CIDP (59), and MGUSP (23) were serially examined (1-year). Predefined arbitrary cut-offs (so-called patients' Functional-Acceptable-Clinical-Thresholds [FACTs]) were taken at the 50th, 75th, and 90th percentile of the Inflammatory-Rasch-built-Overall-Disability-Scale (I-RODS(©) ). We determined the proportion of patients able to walk outside independently that reached the postulated cut-offs. A mean total of 85%, 39%, and 12% of all patients able to walk reached 50th, 75th, and 90th percentile thresholds, respectively. These findings were not neuropathy type related. Our findings show that assessing only one construct of functionality (e.g., walking ability) does not reflect the full scope of daily/social functional deficits perceived by patients. The ability to walk shows a patient is doing better, but not necessarily doing well. The I-RODS(©) bypasses these limitations.

Outcome measures in MMN revisited: further improvement needed.

The objectives of this study were to provide an overview of the outcome measures (OMs) applied in clinical trials in multifocal motor neuropathy (MMN) and to determine the responsiveness of a core set of selected OMs as part of the peripheral neuropathy outcome measures standardization (PeriNomS) study. The following OMs were serially applied in 26 patients with newly diagnosed or relapsing MMN, receiving intravenous immunoglobulin (assessments: T0/T3/T12 months): 14 muscle pairs MRC (Medical Research Council) scale, the Neuropathy Impairment Scale motor-subset, a self-evaluation scale, grip strength, and MMN-RODS© (Rasch-built overall disability scale). All data, except the grip strength, were subjected to Rasch analyses before determining responsiveness. For grip strength, responsiveness was examined using a combined anchor- (SF-36 question-2) and distribution-based (½ × SD) minimum clinically important difference (MCID) techniques, determining the proportion of patients exceeding both the identified cut-offs. For the remaining scales, the magnitude of change for each patient on each scale was determined using the MCID related to the individual SE (responder definition: MCID-SE ≥ 1.96). Overall, a great assortment of measures has been used in MMN trials with different responsiveness definitions. For the selected OMs, responsiveness was poor and only seen in one fourth to one third of the patients, the grip strength being more responsive. Despite the efforts taken to standardize outcome assessment, further clinimetric responsiveness studies are needed in MMN.

Comparing the NIS vs. MRC and INCAT sensory scale through Rasch analyses.

We performed a comparison between Neuropathy Impairment Scale-sensory (NISs) vs. the modified Inflammatory Neuropathy Cause and Treatment sensory scale (mISS), and NIS-motor vs. the Medical Research Council sum score in patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and IgM monoclonal gammopathy of undetermined significance-related polyneuropathy (MGUSP). The ordinal data were subjected to Rasch analyses, creating Rasch-transformed (RT)-intervals for all measures. Comparison between measures was based on validity/reliability with an emphasis on responsiveness (using the patient's level of change related to the individually obtained varying SE for minimum clinically important difference). Eighty stable patients (GBS: 30, CIDP: 30, and MGUSP: 20) were assessed twice (entry: two observers; 2-4 weeks later: one observer), and 137 newly diagnosed or relapsing patients (GBS: 55, CIDP: 59, and IgM-MGUSP: 23) were serially examined with 12 months follow-up. Data modifications were needed to improve model fit for all measures. The sensory and motor scales demonstrated approximately equal and acceptable validity and reliability scores. Responsiveness scores were poor but slightly higher in RT-mISS compared to RT-NISs. Responsiveness was equal for the RT-motor scales, but higher in GBS compared to CIDP; responsiveness was poor in patients with MGUSP, suggesting a longer duration of follow-up in the latter group of patients.

Impairment measures versus inflammatory RODS in GBS and CIDP: a responsiveness comparison.

This study aimed to 'define responder' through the concept of minimum clinically important differences using the individually obtained standard errors (MCID-SE) and a heuristic 'external criterion' responsiveness method in patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). One hundred and fourteen newly diagnosed or relapsing patients (GBS: 55, CIDP: 59) were serially examined (1-year follow-up). The inflammatory Rasch-built overall disability scale (I-RODS), Rasch-transformed MRC sum score (RT-MRC), and Rasch-transformed modified-INCAT-sensory scale (RT-mISS) were assessed. Being-a-responder was defined as having a MCID-SE cut-off ≥1.96. Also, the correlations between patients' scores on each scale and the EuroQoL health-status 'thermometer' (external criterion) were determined (higher correlation indicated better responsiveness). In both diseases, the SEs showed a characteristic 'U'-shaped dynamic pattern across each scales' continuum. The number of patients showing a meaningful change were higher for the I-RODS > RT-MRC > RT-mISS and were in GBS higher than CIDP patients. The MCID-SE concept using Rasch-transformed data demonstrated an individual pattern of 'being-a-responder' in patients with immune-mediated neuropathies, and the findings were validated by the external criterion responsiveness method. The I-RODS showed greater responsiveness compared with the MRC and INCAT-sensory scales, and its use is therefore recommended in future trials in GBS and CIDP.

Grip strength comparison in immune-mediated neuropathies: Vigorimeter vs. Jamar.

The Jamar dynamometer and Vigorimeter have been used to assess grip strength in immune-mediated neuropathies, but have never been compared to each other. Therefore, we performed a comparison study between these two devices in patients with immune-mediated neuropathies. Grip strength data were collected in 102 cross-sectional stable and 163 longitudinal (new diagnoses or changing condition) patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), gammopathy-related polyneuropathy (MGUSP), and multifocal motor neuropathy (MMN). Stable patients were assessed twice (validity/reliability studies). Longitudinal patients were assessed 3-5 times during 1 year. Responsiveness comparison between the two tools was examined using combined anchor-/distribution-based minimum clinically important difference (MCID) techniques. Patients were asked to indicate their preference for the Jamar or Vigorimeter. Both tools correlated highly with each other (ρ = 0.86, p < 0.0001) and showed good intra-class correlation coefficients (Jamar [Right/Left hands]: ICC 0.997/0.96; Vigori: ICC 0.95/0.98). Meaningful changes were comparable between the two instruments, being higher in GBS compared to CIDP patients. In MGUSP/MMN poor responsiveness was seen. Significant more patients preferred the Vigorimeter. In conclusion, validity, reliability, and responsiveness aspects were comparable between the Jamar dynamometer and Vigorimeter. However, based on patients' preference, the Vigorimeter is recommended in future studies in immune-mediated neuropathies.

Exceptionally preserved crustaceans from western Canada reveal a cryptic Cambrian radiation.

The early history of crustaceans is obscured by strong biases in fossil preservation, but a previously overlooked taphonomic mode yields important complementary insights. Here we describe diverse crustacean appendages of Middle and Late Cambrian age from shallow-marine mudstones of the Deadwood Formation in western Canada. The fossils occur as flattened and fragmentary carbonaceous cuticles but provide a suite of phylogenetic and ecological data by virtue of their detailed preservation. In addition to an unprecedented range of complex, largely articulated filtering limbs, we identify at least four distinct types of mandible. Together, these fossils provide the earliest evidence for crown-group branchiopods and total-group copepods and ostracods, extending the respective ranges of these clades back from the Devonian, Pennsylvanian, and Ordovician. Detailed similarities with living forms demonstrate the early origins and subsequent conservation of various complex food-handling adaptations, including a directional mandibular asymmetry that has persisted through half a billion years of evolution. At the same time, the Deadwood fossils indicate profound secular changes in crustacean ecology in terms of body size and environmental distribution. The earliest radiation of crustaceans is largely cryptic in the fossil record, but "small carbonaceous fossils" reveal organisms of surprisingly modern aspect operating in an unfamiliar biosphere.

Sophisticated particle-feeding in a large Early Cambrian crustacean.

Most Cambrian arthropods employed simple feeding mechanisms requiring only low degrees of appendage differentiation. In contrast, post-Cambrian crustaceans exhibit a wide diversity of feeding specializations and possess a vast ecological repertoire. Crustaceans are evident in the Cambrian fossil record, but have hitherto been known exclusively from small individuals with limited appendage differentiation. Here we describe a sophisticated feeding apparatus from an Early Cambrian arthropod that had a body length of several centimetres. Details of the mouthparts resolve this taxon as a probable crown-group (pan)crustacean, while its feeding style, which allowed it to generate and handle fine food particles, significantly expands the known ecological capabilities of Cambrian arthropods. This Early Cambrian record predates the major expansions of large-bodied, particle-handling crustaceans by at least one hundred million years, emphasizing the importance of ecological context in driving adaptive radiations.

Beyond the Burgess Shale: Cambrian microfossils track the rise and fall of hallucigeniid lobopodians.

Burgess Shale-type deposits are renowned for their exquisite preservation of soft-bodied organisms, representing a range of animal body plans that evolved during the Cambrian 'explosion'. However, the rarity of these fossil deposits makes it difficult to reconstruct the broader-scale distributions of their constituent organisms. By contrast, microscopic skeletal elements represent an extensive chronicle of early animal evolution--but are difficult to interpret in the absence of corresponding whole-body fossils. Here, we provide new observations on the dorsal spines of the Cambrian lobopodian (panarthropod) worm Hallucigenia sparsa from the Burgess Shale (Cambrian Series 3, Stage 5). These exhibit a distinctive scaly microstructure and layered (cone-in-cone) construction that together identify a hitherto enigmatic suite of carbonaceous and phosphatic Cambrian microfossils--including material attributed to Mongolitubulus, Rushtonites and Rhombocorniculum--as spines of Hallucigenia-type lobopodians. Hallucigeniids are thus revealed as an important and widespread component of disparate Cambrian communities from late in the Terreneuvian (Cambrian Stage 2) through the 'middle' Cambrian (Series 3); their apparent decline in the latest Cambrian may be partly taphonomic. The cone-in-cone construction of hallucigeniid sclerites is shared with the sclerotized cuticular structures (jaws and claws) in modern onychophorans. More generally, our results emphasize the reciprocal importance and complementary roles of Burgess Shale-type fossils and isolated microfossils in documenting early animal evolution.

Quantitative comparison of geological data and model simulations constrains early Cambrian geography and climate.

Marine ecosystems with a diverse range of animal groups became established during the early Cambrian (~541 to ~509 Ma). However, Earth's environmental parameters and palaeogeography in this interval of major macro-evolutionary change remain poorly constrained. Here, we test contrasting hypotheses of continental configuration and climate that have profound implications for interpreting Cambrian environmental proxies. We integrate general circulation models and geological observations to test three variants of the 'Antarctocentric' paradigm, with a southern polar continent, and an 'equatorial' configuration that lacks polar continents. This quantitative framework can be applied to other deep-time intervals when environmental proxy data are scarce. Our results show that the Antarctocentric palaeogeographic paradigm can reconcile geological data and simulated Cambrian climate. Our analyses indicate a greenhouse climate during the Cambrian animal radiation, with mean annual sea-surface temperatures between ~9 °C to ~19 °C and ~30 °C to ~38 °C for polar and tropical palaeolatitudes, respectively.

Are palaeoscolecids ancestral ecdysozoans?

The reconstruction of ancestors is a central aim of comparative anatomy and evolutionary developmental biology, not least in attempts to understand the relationship between developmental and organismal evolution. Inferences based on living taxa can and should be tested against the fossil record, which provides an independent and direct view onto historical character combinations. Here, we consider the nature of the last common ancestor of living ecdysozoans through a detailed analysis of palaeoscolecids, an early and extinct group of introvert-bearing worms that have been proposed to be ancestral ecdysozoans. In a review of palaeoscolecid anatomy, including newly resolved details of the internal and external cuticle structure, we identify specific characters shared with various living nematoid and scalidophoran worms, but not with panarthropods. Considered within a formal cladistic context, these characters provide most overall support for a stem-priapulid affinity, meaning that palaeoscolecids are far-removed from the ecdysozoan ancestor. We conclude that previous interpretations in which palaeoscolecids occupy a deeper position in the ecdysozoan tree lack particular morphological support and rely instead on a paucity of preserved characters. This bears out a more general point that fossil taxa may appear plesiomorphic merely because they preserve only plesiomorphies, rather than the mélange of primitive and derived characters anticipated of organisms properly allocated to a position deep within animal phylogeny.

Carbonaceous preservation of Cambrian hexactinellid sponge spicules.

Early fossil sponges offer a direct window onto the evolutionary emergence of animals, but insights are limited by the paucity of characters preserved in the conventional fossil record. Here, a new preservational mode for sponge spicules is reported from the lower Cambrian Forteau Formation (Newfoundland, Canada), prompting a re-examination of proposed homologies and sponge inter-relationships. The spicules occur as wholly carbonaceous films, and are interpreted as the remains of robust organic spicule sheaths. Comparable sheaths are restricted among living taxa to calcarean sponges, although the symmetries of the fossil spicules are characteristic of hexactinellid sponges. A similar extinct character combination has been documented in the Burgess Shale fossil Eiffelia. Interpreting the shared characters as homologous implies complex patterns of spicule evolution, but an alternative interpretation as convergent autapomorphies is more parsimonious. In light of the mutually exclusive distributions of these same characters among the crown groups, this result suggests that sponges exhibited an early episode of disparity expansion followed by comparatively constrained evolution, a pattern shared with many other metazoans but obscured by the conventional fossil record of sponges.

Symbiotic fouling of Vetulicola, an early Cambrian nektonic animal.

Here, we report the earliest fossil record to our knowledge of surface fouling by aggregates of small vermiform, encrusting and annulated tubular organisms associated with a mobile, nektonic host, the enigmatic Cambrian animal Vetulicola. Our material is from the exceptionally preserved early Cambrian (Epoch 2, Age 3), Chengjiang biota of Yunnan Province, southwest China, a circa 518 million-year old marine deposit. Our data show that symbiotic fouling relationships between species formed a component of the diversification of animal-rich ecosystems near the beginning of the Phanerozoic Eon, suggesting an early escalation of intimate ecologies as part of the Cambrian animal radiation.

Variation in appendages in early Cambrian bradoriids reveals a wide range of body plans in stem-euarthropods.

Traditionally, the origin and evolution of modern arthropod body plans has been revealed through increasing levels of appendage specialisation exhibited by Cambrian euarthropods. Here we show significant variation in limb morphologies and patterns of limb-tagmosis among three early Cambrian arthropod species conventionally assigned to the Bradoriida. These arthropods are recovered as a monophyletic stem-euarthropod group (and sister taxon to crown-group euarthropods, i.e. Chelicerata, Mandibulata and their extinct relatives), thus implying a radiation of stem-euarthropods where trends towards increasing appendage specialisation were explored convergently with other euarthropod groups. The alternative solution, where bradoriids are polyphyletic, representing several independent origins of a small, bivalved body plan in lineages from diverse regions of the euarthropod and mandibulate stems, is only marginally less parsimonious. The new data reveal a previously unknown disparity of body plans in stem-euarthropods and both solutions support remarkable evolutionary convergence, either of fundamental body plans or appendage specialization patterns.

An early Cambrian greenhouse climate.

The oceans of the early Cambrian (~541 to 509 million years ago) were the setting for a marked diversification of animal life. However, sea temperatures-a key component of the early Cambrian marine environment-remain unconstrained, in part because of a substantial time gap in the stable oxygen isotope (δ18O) record before the evolution of euconodonts. We show that previously overlooked sources of fossil biogenic phosphate have the potential to fill this gap. Pristine phosphatic microfossils from the Comley Limestones, UK, yield a robust δ18O signature, suggesting sea surface temperatures of 20° to 25°C at high southern paleolatitudes (~65°S to 70°S) between ~514 and 509 million years ago. These sea temperatures are consistent with the distribution of coeval evaporite and calcrete deposits, peak continental weathering rates, and also our climate model simulations for this interval. Our results support an early Cambrian greenhouse climate comparable to those of the late Mesozoic and early Cenozoic, offering a framework for exploring the interplay between biotic and environmental controls on Cambrian animal diversification.