The influence of shyness on the use of Facebook in an undergraduate sample

Researchers have suggested that individual differences will help to determine which online communication tools appeal to and are used by different individuals. With respect to the domain of computer-mediated communication, shyness is a particular personality trait of interest, as forums provide opportunities for social interactions that shy individuals might otherwise avoid. The present study investigated the personality trait of shyness and its relation with certain features of an online communication tool (Facebook). We hypothesized that shyness would be significantly related to the quantity of time spent on Facebook, the number of contacts added to one’s Facebook profile, and attitudes toward Facebook. Our findings supported that shyness was significantly positively correlated with the time spent on Facebook and having favorable attitudes toward the social networking site. Furthermore, shyness was significantly negatively correlated with the number of Facebook “Friends.” Limitations of the present study and suggestions for future research are addressed

Bryozoan genera Fenestrulina and Microporella no longer confamilial; multi-gene phylogeny supports separation

Bryozoans are a moderately diverse, mostly marine phylum with a fossil record extending to the early Ordovician. Compared to other phyla, little is known about their phylogenetic relationships at both lower and higher taxonomic levels. Hence, an effort is being made to elucidate the phylogenetic relationships among bryozoans. Here, we present newly sequenced nuclear and mitochondrial genes for 21 cheilostome bryozoans and compile these with existing orthologous molecular data. Using these data, we focus on reconstructing the phylogenetic relationships of Fenestrulina and Microporella, two species-rich genera. They are currently placed in a globally distributed family, Microporellidae, defined by having a semicircular primary orifice and a proximal ascopore, although there are indirect inferences in the morphological literature that suggest they might not be confamilial. Our six-gene phylogenetic analysis reveals that the genera Fenestrulina and Microporella are each monophyletic, with the sister clade to Microporella comprising non-microporellids. These genera thus have a polyphyletic relationship and should not be placed in the same family. Our result supports the reinstatement of the family Fenestrulinidae Jullien, 1888 for Fenestrulina and genera with comparable frontal shield and ooecial morphologies. Our well-supported phylogeny based on independent molecular data lends credit to existing phylogenetic hypotheses based on morphological observations but does not conform to the current classification of these particular bryozoans. This illustrates the general need for a rethink of bryozoan higher-level systematics, ideally based on both morphological and molecular data

Efficacy of probucol on cognitive function in Alzheimer's disease: study protocol for a double-blind, placebo-controlled, randomised phase II trial (PIA study).

INTRODUCTION: Preclinical, clinical and epidemiological studies support the hypothesis that aberrant systemic metabolism of amyloid beta (Aβ) in the peripheral circulation is causally related to the development of Alzheimer's disease (AD). Specifically, recent studies suggest that increased plasma concentrations of lipoprotein-Aβ compromise the brain microvasculature, resulting in extravasation and retention of the lipoprotein-Aβ moiety. The latter results in an inflammatory response and neurodegeneration ensues. Probucol, a historic cholesterol-lowering drug, has been shown in murine models to suppress lipoprotein-Aβ secretion, concomitant with maintaining blood-brain-barrier function, suppressing neurovascular inflammation and supporting cognitive function. This protocol details the probucol in Alzheimer's study, a drug intervention trial investigating if probucol has potential to attenuate cognitive decline, delay brain atrophy and reduce cerebral amyloid burden in patients with mild-to-moderate AD. METHODS AND ANALYSIS: The study is a phase II, randomised, placebo-controlled, double-blind single-site clinical trial held in Perth, Australia. The target sample is 314 participants with mild-to-moderate AD. Participants will be recruited and randomised (1:1) to a 104-week intervention consisting of placebo induction for 2 weeks followed by 102 weeks of probucol (Lorelco) or placebo. The primary outcome is changed in cognitive performance determined via the Alzheimer's Disease Assessment Scales-Cognitive Subscale test between baseline and 104 weeks. Secondary outcomes measures will be the change in brain structure and function, cerebral amyloid load, quality of life, and the safety and tolerability of Lorelco, after a 104week intervention. ETHICS AND DISSEMINATION: The study has been approved by the Bellberry Limited Human Research Ethics Committee (approval number: HREC2019-11-1063; Version 4, 6 October 2021). Informed consent will be obtained from participants prior to any study procedures being performed. The investigator group will disseminate study findings through peer-reviewed publications, key conferences and local stakeholder events. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12621000726853)

Systematic Dissection and Trajectory-Scanning Mutagenesis of the Molecular Interface That Ensures Specificity of Two-Component Signaling Pathways

Two-component signal transduction systems enable bacteria to sense and respond to a wide range of environmental stimuli. Sensor histidine kinases transmit signals to their cognate response regulators via phosphorylation. The faithful transmission of information through two-component pathways and the avoidance of unwanted cross-talk require exquisite specificity of histidine kinase-response regulator interactions to ensure that cells mount the appropriate response to external signals. To identify putative specificity-determining residues, we have analyzed amino acid coevolution in two-component proteins and identified a set of residues that can be used to rationally rewire a model signaling pathway, EnvZ-OmpR. To explore how a relatively small set of residues can dictate partner selectivity, we combined alanine-scanning mutagenesis with an approach we call trajectory-scanning mutagenesis, in which all mutational intermediates between the specificity residues of EnvZ and another kinase, RstB, were systematically examined for phosphotransfer specificity. The same approach was used for the response regulators OmpR and RstA. Collectively, the results begin to reveal the molecular mechanism by which a small set of amino acids enables an individual kinase to discriminate amongst a large set of highly-related response regulators and vice versa. Our results also suggest that the mutational trajectories taken by two-component signaling proteins following gene or pathway duplication may be constrained and subject to differential selective pressures. Only some trajectories allow both the maintenance of phosphotransfer and the avoidance of unwanted cross-talk

Decoding human fetal liver haematopoiesis.

Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 140,000 liver and 74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the influence of the tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, natural killer and innate lymphoid cell precursors in the yolk sac. We demonstrate a shift in the haemopoietic composition of fetal liver during gestation away from being predominantly erythroid, accompanied by a parallel change in differentiation potential of HSC/MPPs, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a reference for harnessing the therapeutic potential of HSC/MPPs.We acknowledge funding from the Wellcome Human Cell Atlas Strategic Science Support (WT211276/Z/18/Z); M.H. is funded by Wellcome (WT107931/Z/15/Z), The Lister Institute for Preventive Medicine and NIHR and Newcastle-Biomedical Research Centre; S.A.T. is funded by Wellcome (WT206194), ERC Consolidator and EU MRG-Grammar awards and; S.B. is funded by Wellcome (WT110104/Z/15/Z) and St. Baldrick’s Foundation; E.L. is funded by a Wellcome Sir Henry Dale and Royal Society Fellowships, European Haematology Association, Wellcome and MRC to the Wellcome-MRC Cambridge Stem Cell Institute and BBSRC

Hypusine biosynthesis in β cells links polyamine metabolism to facultative cellular proliferation to maintain glucose homeostasis

Deoxyhypusine synthase (DHPS) utilizes the polyamine spermidine to catalyze the hypusine modification of the mRNA translation factor eIF5A and promotes oncogenesis through poorly-defined mechanisms. Because germline deletion of Dhps is embryonically lethal, its role in normal postnatal cellular function in vivo remains unknown. We generated a mouse model that enabled the inducible, postnatal deletion of Dhps specifically in postnatal islet β cells, which function to maintain glucose homeostasis. Removal of Dhps did not have an effect under normal physiologic conditions. However, upon development of insulin resistance, which induces β-cell proliferation, Dhps deletion caused alterations in proteins required for mRNA translation and protein secretion, reduced production of the cell cycle molecule cyclin D2, impaired β-cell proliferation, and induced overt diabetes. We found that hypusine biosynthesis was downstream of protein kinase C-ζ and was required for c-Myc-induced proliferation. Our studies reveal a requirement for DHPS in β cells to link polyamines to mRNA translation to effect facultative cellular proliferation and glucose homeostasis

Quantifying the controls of Peruvian glacier response to climate

Peruvian glaciers are important contributors to dry season runoff for agriculture and hydropower, but they are at risk of disappearing due to climate warming. Their energy balance and ablation characteristics have previously been studied only for individual glaciers, with no comparisons between regions. We applied the physically-based, energy balance melt component of the model Tethys-Chloris at five on-glacier meteorological stations: three in the Cordillera Blanca near Huaraz (with glaciers above ~4300 m a.s.l.), and two in the Cordillera Vilcanota east of Cusco (with glaciers above ~ 4800 m). The climate of these regions is strongly seasonal, with an austral summer wet season and winter dry season. Our results revealed that at most sites the energy available for melt is greatest in the wet season. This is a consequence of the dry season energy losses from the latent heat flux and net longwave radiation which counter-balance the high dry season net shortwave radiation, which otherwise dominates the energy balance. The sensible heat flux is a relatively small contributor to melt energy in both seasons. Comparison of the five sites suggests that there is more energy available for melt at a given elevation in the Cordillera Vilcanota compared to the Cordillera Blanca. At three of the sites the wet season snowpack was discontinuous, forming and melting within a daily to weekly timescale. Albedo and melt are thus highly variable in the wet season and closely related to the precipitation dynamics. At the highest site, in the accumulation zone of the Quelccaya Ice Cap, 81% of ablation was from sublimation. Sublimation was less important at the lower sites, but it reduces dry season melt. Correlation of the NOAA Oceanic El Niño Index (ONI) to the outputs of the two sites with the longest records revealed that the warmer wet season temperatures characteristic of a positive ONI were associated with a decreased albedo, greater net shortwave radiation, a more positive sensible heat flux and increased melt rates. Air temperature and precipitation inputs were also perturbed at all five sites to understand their sensitivity to climate change. Enhanced mass loss was predicted with a static increase of 2°C or more, even with a +30% precipitation increase, with the lower elevation Cordillera Blanca sites at risk of the greatest mass loss due to warming

High-Frequency Dynamics of Ocean pH: A Multi-Ecosystem Comparison

The effect of Ocean Acidification (OA) on marine biota is quasi-predictable at best. While perturbation studies, in the form of incubations under elevated pCO2, reveal sensitivities and responses of individual species, one missing link in the OA story results from a chronic lack of pH data specific to a given species' natural habitat. Here, we present a compilation of continuous, high-resolution time series of upper ocean pH, collected using autonomous sensors, over a variety of ecosystems ranging from polar to tropical, open-ocean to coastal, kelp forest to coral reef. These observations reveal a continuum of month-long pH variability with standard deviations from 0.004 to 0.277 and ranges spanning 0.024 to 1.430 pH units. The nature of the observed variability was also highly site-dependent, with characteristic diel, semi-diurnal, and stochastic patterns of varying amplitudes. These biome-specific pH signatures disclose current levels of exposure to both high and low dissolved CO2, often demonstrating that resident organisms are already experiencing pH regimes that are not predicted until 2100. Our data provide a first step toward crystallizing the biophysical link between environmental history of pH exposure and physiological resilience of marine organisms to fluctuations in seawater CO2. Knowledge of this spatial and temporal variation in seawater chemistry allows us to improve the design of OA experiments: we can test organisms with a priori expectations of their tolerance guardrails, based on their natural range of exposure. Such hypothesis-testing will provide a deeper understanding of the effects of OA. Both intuitively simple to understand and powerfully informative, these and similar comparative time series can help guide management efforts to identify areas of marine habitat that can serve as refugia to acidification as well as areas that are particularly vulnerable to future ocean change