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The P522R variant of PLCG2, expressed by microglia, is associated with reduced risk of Alzheimer's disease (AD). Yet, the impact of this protective mutation on microglial responses to AD pathology remains unknown. Chimeric AD and wild‐type mice were generated by transplanting PLCG2‐P522R or isogenic wild‐type human induced pluripotent stem cell microglia. At 7 months of age, single‐cell and bulk RNA sequencing, and histological analyses were performed. The PLCG2‐P522R variant induced a significant increase in microglial human leukocyte antigen (HLA) expression and the induction of antigen presentation, chemokine signaling, and T cell proliferation pathways. Examination of immune‐intact AD mice further demonstrated that the PLCG2‐P522R variant promotes the recruitment of CD8+ T cells to the brain. These data provide the first evidence that the PLCG2‐P522R variant increases the capacity of microglia to recruit T cells and present antigens, promoting a microglial transcriptional state that has recently been shown to be reduced in AD patient brains. [ABSTRACT FROM AUTHOR]

The impact of language interpretation on interactive communication in genetic counseling sessions is not well studied. We sought to determine whether interpretation affects communication in genetic counseling sessions using communication analysis. With a sample of pregnant patients of advanced maternal age, we audiotaped, analyzed, and compared seven Spanish‐speaking patients with limited‐English proficiency to seven English‐speaking patients on length of session, English words spoken, and number of questions asked. An analysis of verbal listening cues, including back‐channels and questions asked was performed to evaluate the level of engagement by both provider and patient. Session length did not differ between groups (p > 0.05), however, English‐speaking sessions involved significantly more words (mean: 4,798 vs. 2,524) exchanged over the course of the conversation than interpreter‐mediated sessions (p < 0.001). The number of back‐channeling responses was significantly greater in English‐speaking compared to Spanish‐speaking sessions. We found the same information was covered, but there was less provider–patient interaction when the session was interpreter‐mediated. The patient asked fewer questions and the genetic counselor spoke in condensed ideas. Overall, our observations suggest diminished levels of interactive communication in interpreter‐mediated sessions. Our work highlights the need for further evaluation in how genetic counselors communicate during interpreter‐mediated sessions. [ABSTRACT FROM AUTHOR]

Abstract: In this short review, we highlight recent findings in the emerging field of epitranscriptomic mechanisms and discuss their potential role in neural plasticity, learning and memory. These include the influence of RNA modifications on activity‐induced RNA structure states, RNA editing and RNA localization, and how qualitative state changes in RNA increase the functional diversity and information‐carrying capacity of RNA molecules. We predict that RNA modifications may be just as important for synaptic plasticity and memory as quantitative changes in transcript and protein abundance, but with the added advantage of not being required to signal back to the nucleus, and therefore better suited to be coordinated with the temporal dynamics of learning. [ABSTRACT FROM AUTHOR]

Questions Why does bryophyte richness increase along the elevational gradient? Even though a number of studies have documented the peculiar positive (or hump-shaped) relationship between species richness and elevation in bryophytes, it is still unclear which underlying mechanisms cause the pattern. Location Norway spruce forests, Italian Alps, South Tyrol. Methods Eight gradients from 900 to 1900 m a.s.l. and three different substrata (forest floor, deadwood, tree trunks) were examined. Three responses from the bryophyte communities were analysed: species richness of mosses and liverworts, functional diversity (considering the morphological characteristics of species) and β-diversity (separating the two components: richness difference and species turnover). Results On deadwood and tree trunks a quadratic relationship was found between bryophyte richness and elevation, but not on the forest floor. On all three substrata, the moss assemblages along the elevational gradient were dominated by the turnover process and not by the richness component of β-diversity. In liverworts, the two components of β-diversity were equally important. Temperature was the most important predictor of bryophyte richness, whereas model selection suggested that temperature, solar radiation and rainfall had equal effects on functional diversity. Conclusions The substrata affect the response of bryophytes to the elevational gradient. The bryophyte assemblages inhabiting the forest floor, being less subject to climatic variability than deadwood and tree trunks, could be less affected by the temperature increase where climate change is occurring. [ABSTRACT FROM AUTHOR]

Many variants of uncertain functional significance in cancer susceptibility genes lie in regulatory regions, and clarifying their association with disease risk poses significant challenges. We studied 17 germline variants (nine of which were novel) in the CDKN2A 5′ UTR with independent approaches, which included mono and bicistronic reporter assays, Western blot of endogenous protein, and allelic representation after polysomal profiling to investigate their impact on CDKN2A mRNA translation regulation. Two of the novel variants (c.-27del23, c.-93-91del AGG) were classified as causal mutations (score ≥3), along with the c.-21C>T, c.-34G>T, and c.-56G>T, which had already been studied by a subset of assays. The novel c.-42T>A as well as the previously described c.-67G>C were classified as potential mutations (score 1 or 2). The remaining variants (c.-14C>T, c.-20A>G, c.-25C>T+c.-180G>A, c.-30G>A, c.-40C>T, c.-45G>A, c.-59C>G, c.-87T>A, c.-252A>T) were classified as neutral (score 0). In conclusion, we found evidence that nearly half of the variants found in this region had a negative impact on CDKN2A mRNA translation, supporting the hypothesis that 5′ UTR can act as a cellular Internal Ribosome Entry Site ( IRES) to modulate p16 INK 4a translation. [ABSTRACT FROM AUTHOR]

The advent of deep sequencing technology has unexpectedly advanced our structural understanding of molecules composed of nucleic acids. A significant amount of progress has been made recently extrapolating the chemical methods to probe RNA structure into sequencing methods. Herein we review some of the canonical methods to analyze RNA structure, and then we outline how these have been used to probe the structure of many RNAs in parallel. The key is the transformation of structural biology problems into sequencing problems, whereby sequencing power can be interpreted to understand nucleic acid proximity, nucleic acid conformation, or nucleic acid-protein interactions. Utilizing such technologies in this way has the promise to provide novel structural insights into the mechanisms that control normal cellular physiology and provide insight into how structure could be perturbed in disease. [ABSTRACT FROM AUTHOR]

Aim Detailed knowledge of species distributions, endemism patterns and threats is critical to site prioritization and conservation planning. However, data from biodiversity inventories are still limited, especially for tropical forests, and even well recognized hotspots remain understudied. We provide an example of how updated knowledge on species occurrence from strategically directed biodiversity surveys can change knowledge on perceived biodiversity importance, and facilitate understanding diversity patterns and the delivery of conservation recommendations. Location Eastern Arc Mountains ( EAM), Kenya and Tanzania. Methods We surveyed amphibians, reptiles, birds and mammals during 2005-2009, targeting mountain blocks that had been poorly surveyed or unsurveyed by the early Noughties. We combined new and old data to produce a database of species presence by mountain block spanning four decades of research. Species richness is regressed against survey effort, funding, ecological and human disturbance factors to analyse the best predictors of vertebrate richness across mountain blocks. Similarity among species assemblages among blocks is analysed using dissimilarity analysis. Results New surveys raised the number of endemic and regional endemic vertebrates by 24% (from 170 to 211 species), including 27 new species of which 23 are amphibians and reptiles. Vertebrate richness is best explained by forest area, but rainfall is also important, especially for amphibians and reptiles. Forest elevational range is important for mammals and for block-endemic birds. Funding explains 19% of the variation in total species richness, while survey effort generally explains < 10% of variance. Cluster analysis shows that species assemblages are partitioned by geographical proximity among mountain blocks. Main conclusions The biological value of the EAM has been underestimated, and strategic surveys are important even in well-recognized hotspots. The exceptional and global importance of these mountains for endemic vertebrates is highlighted, supporting the development of a network of Nature Reserves and the proposed inclusion within UNESCO's natural World Heritage Sites. [ABSTRACT FROM AUTHOR]

Bangia atropurpurea (Mertens ex Roth) C. Agardh is a freshwater red alga species that is distributed worldwide. B. atropurpurea is highly adaptable due to its stress-tolerance, which ensures survival under desiccation periods and under radiation extremes typical of the supra- and upper eulittoral zones. Whereas a number of previous investigations addressed some of the physiological and biochemical traits involved in stress-tolerance, we studied the spatial arrangement of the mature (multiseriate) and immature (uniseriate) filaments and of selected bioorganic compounds along a gradient defined by distance from the waterline. Substantial physiological and biochemical differences were previously observed among phenological stages in the marine environment. In this study, we showed a nonrandom spatial structure of both phenological stages and photosynthetic pigments and photoprotective compounds, R-phycocyanin and R-phycoerythrin along the supralittoral-eulittoral gradient. This observed pattern strongly suggests a complex interplay between physio-morphological regulation and spatial arrangement of mature and immature filaments in conferring the typical stress tolerance of B. atropurpurea. [ABSTRACT FROM AUTHOR]

Although mosses and lichens are a relevant component of the biota of rock habitats targeted for biodiversity conservation in Europe, the ecological factors driving their distribution are still poorly known. In this work, we examined the epilithic moss and lichen assemblages colonizing boulders of different types of calcareous rocks co-occurring in the same area in the Italian Alps. The goals were: (1) to evaluate if and to what extent different calcareous rocks host different assemblages; (2) to identify species associated to each rock type; (3) to quantify the relative importance of rock type, local environmental factors, and habitat spatial structure in explaining species distribution. Our results demonstrated that different calcareous rocks host different moss and lichen assemblages with some typical species, indicating that each rock type contributes to the total diversity of both mosses and lichens. Local environmental conditions influenced mosses and not lichens whose distribution is mainly associated to rock type. The patterns of both organism groups were also significantly related to habitat spatial structure, species assemblages tending to have a patchy distribution, which may reflect dispersal dynamics. Our results have implications for conservation: (1) each rock type may play a relevant role in maintaining the overall diversity contributing with unique assemblages and typical species; (2) the patchy distribution of both moss and lichen assemblages should warn from considering rock patches as a monotonous repetition of the same habitat across space. [ABSTRACT FROM AUTHOR]

While the effects of contemporaneous local environment on species richness have been repeatedly documented, much less is known about historical effects, especially over large temporal scales. Using fen sites in the Western Carpathian Mountains with known radiocarbon-dated ages spanning Late Glacial to modern times (16?975-270 cal years before 2008), we have compiled richness data from the same plots for three groups of taxa with contrasting dispersal modes: (1) vascular plants, which have macroscopic propagules possessing variable, but rather low, dispersal abilities; (2) bryophytes, which have microscopic propagules that are readily transported long distances by air; and (3) terrestrial and freshwater mollusks, which have macroscopic individuals with slow active migration rates, but which also often possess high passive dispersal abilities. Using path analysis we tested the relationships between species richness and habitat age, area, isolation, and altitude for these groups. When only matrix-derived taxa were considered, no significant positive relation was noted between species richness and habitat size or age. When only calcareous-fen specialists were considered, however, habitat age was found to significantly affect vascular plant richness and, marginally, also bryophyte richness, whereas mollusk richness was significantly affected by habitat area. These results suggest that in inland insular systems only habitat specialist (i.e., interpatch disperser and/or relict species) richness is influenced by habitat age and/or area, with habitat age becoming more important as species dispersal ability decreases. [ABSTRACT FROM AUTHOR]

BACKGROUND: At present, thyroid fine-needle aspiration (FNA) specimens are diagnosed using a tiered classification scheme, with the most popular of these being the 5-tiered and 6-tiered systems. In this study, the authors present their institutional experiences using these 2 different systems and evaluate their efficacy based on the surgical follow-up. METHODS: Thyroid FNA specimens and their corresponding surgical resection specimens were collected between 2007 and 2009. The following diagnostic categories are used in both systems: unsatisfactory/nondiagnostic, benign, follicular neoplasm/suspicious for follicular neoplasm, suspicious for malignancy, and malignant. An additional category termed atypia of undetermined significance/follicular lesion of undetermined significance was used for atypical cases in the 6-tiered system. Statistical analysis was performed by comparing the different diagnostic categories. RESULTS: The case cohort included a total of 7686 thyroid FNA specimens representing 3962 nodules and 3724 nodules, respectively, in the 5-tiered and 6-tiered systems. Negative predictive values for the benign categories (96.9% vs 97.5%; P = 1) and positive predictive values for both the follicular neoplasm categories (26.5% vs 32.1%; P = .2531) and the malignant categories (99.1% vs 99.4%; P = 1) were similar. The most significant differences between the 5-tiered and 6-tiered systems were the percentage of cases classified as benign (83.9% vs 55.4%; P < .0001) and as follicular neoplasms (4.6% vs 23.8%; P < .0001). It is interesting to note that fewer patients were referred for surgery in the 5-tiered system compared with the 6-tiered one (9.1% vs 36.5%; P < .0001). CONCLUSIONS: Use of either the 5-tiered or 6-tiered reporting systems for thyroid FNA specimens can potentially affect the clinical management of patients with thyroid nodules. Cancer (Cancer Cytopathol) 2012. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

In this paper, we present a low-voltage low-dropout voltage regulator (LDO) for a system-on-chip (SoC) application which, exploiting the multiplication of the Miller effect through the use of a current amplifier, is frequency compensated up to 1-nF capacitive load. The topology and the strategy adopted to design the LDO and the related compensation frequency network are described in detail. The LDO works with a supply voltage as low as 1.2 V and provides a maximum load current of 50 mA with a drop-out voltage of 200 mV: the total integrated compensation capacitance is about 40 pF. Measurement results as well as comparison with other SoC LDOs demonstrate the advantage of the proposed topology. [ABSTRACT FROM AUTHOR]

Height above water table in aquatic habitats has long been recognized as the key factor for determining the spatial structure of bryophyte assemblages. Using photosynthetic pigments as indicators of stress along a wet-to-dry gradient, I tested whether different habitat preferences were revealed. A field experiment was set up to obtain a semi-natural hydrological gradient. The spatial distribution of species was quantified by determining the pigment content in natural assemblages and by applying the regression equations derived from the experimental manipulation. The species were able to move water in quantities that were statistically significantly different from each other, which was in agreement with the species characteristics and the colony architectures. Photosynthetic pigments responded in a complex way to the water gradient and, for each species, one or more stress indicators were reliable. A wide overlapping of spatial distribution exists in natural conditions, especially in complex habitats like springs. Although in this study a restricted selection of species has been examined, the method proposed to evaluate the theoretical height above water table is coherent with the broad spatial pattern observed. This approach may be particularly useful for understanding both the coexistence of similar species and the spatial distributions of bryophytes in spring habitats in relation to water stress tolerance. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to develop and evaluate a structural equation model explaining the species richness of bryophytes and vascular plants along multiple environmental gradients. Our primary interests in developing this model were: (1) to evaluate the effect of tree canopy along an altitudinal gradient on bryophyte and vascular plant richness; (2) to determine to what extent lithology was able to explain richness in the two groups of plants; (3) to assess whether anthropogenic disturbances decrease richness; and (4) to explore, comparing competing models, the causal links connecting spring area, discharge and spring complexity and to assess how these variables are related to richness. Location Eighty-six springs were sampled in the south-eastern Alps of Italy, from the lowlands to high-mountain regions, and on different lithologies. Methods A structural equation model (SEM) was used to test certain hypotheses about the direct and indirect effects of altitude, canopy, lithology, disturbance, spring complexity, discharge and spring area on bryophyte and vascular plant richness. Competing models were evaluated and bootstrap simulation was used to determine the stability of parameter estimates. Results SEM analysis made it possible to disentangle the different effects of canopy and lithology on bryophyte and vascular plant richness: for the former it was demonstrated that the increased richness with altitude was related primarily to lithology, whereas the latter increased because of the reduction of canopy cover. In addition, the model predicted that spring discharge determined the size of the spring area and even the complexity of the spring; these latter two variables influenced to different degrees both bryophyte and vascular plant richness. Anthropogenic disturbances affected the richness of bryophytes more than that of the vascular plants. Main conclusions Our study demonstrates that several similarities in the patterns of bryophyte and vascular plant richness are in fact induced by different environmental variables. [ABSTRACT FROM AUTHOR]

The hairpin ribozyme is a small catalytic RNA comprising two helix–loop–helix domains linked by a four-way helical junction (4WJ). In its most basic form, each domain can be formed independently and reconstituted without a 4WJ to yield an active enzyme. The production of such minimal junctionless hairpin ribozymes is achievable by chemical synthesis, which has allowed structures to be determined for numerous nucleotide variants. However, abasic and other destabilizing core modifications hinder crystallization. This investigation describes the use of a dangling 5′-U to form an intermolecular U·U mismatch, as well as the use of synthetic linkers to tether the loop A and B domains, including (i) a three-carbon propyl linker (C3L) and (ii) a nine-atom triethylene glycol linker (S9L). Both linker constructs demonstrated similar enzymatic activity, but S9L constructs yielded crystals that diffracted to 2.65 Å resolution or better. In contrast, C3L variants diffracted to 3.35 Å and exhibited a 15 Å expansion of the c axis. Crystal packing of the C3L construct showed a paucity of 61 contacts, which comprise numerous backbone to 2′-OH hydrogen bonds in junctionless and S9L complexes. Significantly, the crystal packing in minimal structures mimics stabilizing features observed in the 4WJ hairpin ribozyme structure. The results demonstrate how knowledge-based design can be used to improve diffraction and overcome otherwise destabilizing defects. [ABSTRACT FROM AUTHOR]

The authors reflect on the emerging functions of long non-coding RNAs (IncRNAs) in skin biology. Topics discussed include the diverse regulatory mechanisms of IncRNAs, the need for further study to understand the extent and specificity of its expression across skin cell types and compartments and its therapeutic potential in skin diseases.