Buffering and Amplifying Transcriptional Noise During Cell Fate Specification

The molecular processes that drive gene transcription are inherently noisy. This noise often manifests in the form of transcriptional bursts, producing fluctuations in gene activity over time. During cell fate specification, this noise is often buffered to ensure reproducible developmental outcomes. However, sometimes noise is utilized as a “bet-hedging” mechanism to diversify functional roles across a population of cells. Studies of bacteria, yeast, and cultured cells have provided insights into the nature and roles of noise in transcription, yet we are only beginning to understand the mechanisms by which noise influences the development of multicellular organisms. Here we discuss the sources of transcriptional noise and the mechanisms that either buffer noise to drive reproducible fate choices or amplify noise to randomly specify fates

Effects of Carpal Tunnel Syndrome on Dexterous Manipulation Are Grip Type-Dependent

Carpal tunnel syndrome (CTS) impairs sensation of a subset of digits. Although the effects of CTS on manipulation performed with CTS-affected digits have been studied using precision grip tasks, the extent to which CTS affects multi-digit force coordination has only recently been studied. Whole-hand manipulation studies have shown that CTS patients retain the ability to modulate multi-digit forces to object mass, mass distribution, and texture. However, CTS results in sensorimotor deficits relative to healthy controls, including significantly larger grip force and lower ability to balance the torques generated by the digits. Here we investigated the effects of CTS on multi-digit force modulation to object weight when manipulating an object with a variable number of fingers. We hypothesized that CTS patients would be able to modulate digit forces to object weight. However, as different grip types involve the exclusive use of CTS-affected digits (‘uniform’ grips) or a combination of CTS-affected and non-affected digits (‘mixed’ grips), we addressed the question of whether ‘mixed’ grips would reduce or worsen CTS-induced force coordination deficits. The former scenario would be due to adding digits with intact tactile feedback, whereas the latter scenario might occur due to a potentially greater challenge for the central nervous system of integrating ‘noisy’ and intact tactile feedback. CTS patients learned multi-digit force modulation to object weight regardless of grip type. Although controls exerted the same total grip force across all grip types, patients exerted significantly larger grip force than controls but only for manipulations with four and five digits. Importantly, this effect was due to CTS patients’ inability to change the finger force distribution when adding the ring and little fingers. These findings suggest that CTS primarily challenges sensorimotor integration processes for dexterous manipulation underlying the coordination of CTS-affected and non-affected digits

Folian-cv1 Is a Member of a Highly Acidic Phosphoprotein Class Derived From the Foliated Layer of the Eastern Oyster (\u3ci\u3eCrassostrea virginica\u3c/i\u3e) Shell and Identified in Hemocytes and Mantle

The proteins derived from the foliated shell layer of the oyster, Crassostrea virginica, are unusually acidic and highly phosphorylated. Here we report the identification of a gene encoding a member of this class of phosphoproteins that we collectively refer to as folian. Using an in silico approach, a virtual probe was constructed from an N-terminal sequence (DEADAGD) determined for a 48 kDa folian phosphoprotein and used to screen an oyster EST databank. A sequence that matched the N-terminus of the 48 kDa protein was found and used to identify the full-length gene from a C. virginica BAC library. The molecular weight of the deduced gene product is 32 kDa and was named folian-cv1. Genomic Southern analysis revealed two variants of the gene. The mature protein is composed of 43.3% Asp, 32.6% Ser, and 9.1% Glu with 37.5% of the amino acids of the protein potentially phosphorylated. The primary sequence of folian-cv1 is organized in blocks, with a short relatively hydrophobic block at the N-terminus and with the remainder containing low complexity regions largely dominated by aspartic acid and serine. Overall, the protein is predicted to be highly disordered. PCR and sequence analyses identified folian-cv1 expression in the mantle and hemocytes. Immuno-histochemical staining of mantle tissue reveals that cells of the shell-facing epithelium and in the periostracal groove secrete a continuous layer of folian-positive material and that folian-positive hemocytes move through the mantle epithelium. The function in shell formation of folian proteins including folian-cv1 is not known. However, based on the complexity of this class of proteins and the two methods of their delivery to the region of shell formation, it is possible they are involved in diverse ways in this process

Effects of Carpal Tunnel Syndrome on adaptation of multi-digit forces to object mass distribution for whole-hand manipulation

Background Carpal tunnel syndrome (CTS) is a compression neuropathy of the median nerve that results in sensorimotor deficits in the hand. Until recently, the effects of CTS on hand function have been studied using mostly two-digit grip tasks. The purpose of this study was to investigate the coordination of multi-digit forces as a function of object center of mass (CM) during whole-hand grasping. Methods Fourteen CTS patients and age- and gender-matched controls were instructed to grasp, lift, hold, and release a grip device with five digits for seven consecutive lifts while maintaining its vertical orientation. The object CM was changed by adding a mass at different locations at the base of the object. We measured forces and torques exerted by each digit and object kinematics and analyzed modulation of these variables to object CM at object lift onset and during object hold. Our task requires a modulation of digit forces at and after object lift onset to generate a compensatory moment to counteract the external moment caused by the added mass and to minimize object tilt. Results We found that CTS patients learned to generate a compensatory moment and minimized object roll to the same extent as controls. However, controls fully exploited the available degrees of freedom (DoF) in coordinating their multi-digit forces to generate a compensatory moment, i.e., digit normal forces, tangential forces, and the net center of pressure on the finger side of the device at object lift onset and during object hold. In contrast, patients modulated only one of these DoFs (the net center of pressure) to object CM by modulating individual normal forces at object lift onset. During object hold, however, CTS patients were able to modulate digit tangential force distribution to object CM. Conclusions Our findings suggest that, although CTS did not affect patients’ ability to perform our manipulation task, it interfered with the modulation of specific grasp control variables. This phenomenon might be indicative of a lower degree of flexibility of the sensorimotor system in CTS to adapt to grasp task conditions

Foraging behaviour of black guillemots at three Norwegian sites during the breeding season

The intensifcation of coastal development poses potential threats for coastal seabirds, and understanding their habitat use is a key factor to guide conservation and management. In sub-arctic areas, black guillemots (Cepphus grylle) use coastal habitats year-round, which makes them vulnerable to the increasing human activities in these areas. In mainland Norway, one of the species’ strongholds, black guillemots are red-listed after substantial population declines. However, their fnescale foraging behaviour has received little attention to date. We collected and analysed GPS tracking data from adult black guillemots at three sites located over a latitudinal gradient of 250 km in central/northern Norway. Maximum foraging ranges of 33 km at Sklinna (65°12′N) for incubating birds, and 18 km at both Vega (65°34′N) and Sklinna for chick-rearing birds, are among the longest reported for this species. At all three sites, foraging probability was highest in shallow waters (<50 m depth) close to the colony and declined with increasing water depth and distance from colony. However, birds from Vega also foraged over deeper waters. Kelp presence was of high importance at Sklinna, but apparently less important at Røst (67°26’N) and Vega. We also found distinct diferences in foraging activity across the day and with tidal height among the sites. Inter-site diferences in habitat use and foraging activity may be explained by diferences in the availability of habitats and suitable prey. Our study highlights the importance of shallow marine areas for black guillemots and shows that habitat use can vary substantially between sites. Cepphus grylle · Marine spatial planning · Habitat use · Species distribution model · Kelp forestpublishedVersio

A Taxonomy of Extended Radio Sources in Clusters of Galaxies

At the request of the conference attendees, we have compiled a classification of extended radio sources in clusters. These range from scales of tens of parsecs to over a megaparsec in scale, and include both sources associated with AGN and sources thought to derive from the electron population in the ionized ICM. We pay special attention to distinguishing between the types of AGN in the cores of cooling flow clusters and between the multiple classes of objects referred to over the years as ``radio relics.'' We suggest new names based on physical arguments for some of these classes of objects where their commonly used names are inappropriate or confusing.Comment: 5 pages, to appear in "The Riddle of Cooling Flows in Galaxies and Clusters of Galaxies," held in Charlottesvile, VA, May 31 - June 4, 2003, ed. T. H. Reiprich, J. C. Kempner, and N. Soker, http://www.astro.virginia.edu/coolflow

Support-seeking by cancer caregivers living in rural Australia

Objective: Rural cancer caregivers report poor wellbeing and high unmet needs for support. This study investigates sources of support sought by cancer caregivers living in rural Australia, and factors associated with support-seeking. Methods: Informal caregivers of people with cancer completed a questionnaire assessing sociodemographic characteristics, caregiver factors and support-seeking. Descriptive statistics, bivariate analyses and logistic regression were used to identify common sources of support and factors associated with support-seeking. Alluvial and radar plots were used to identify and describe support-seeking profiles. Findings: Of 244 rural caregivers, 64 % reported seeking support for themselves, 72 % for the cancer patient, and 22 % did not seek any support. The most common sources of support were general practitioners and online. Higher caregiver burden, higher income, caring for someone with anxiety/depression or caring for someone who has difficulty completing their usual activities were associated with seeking support from a greater number of sources. The ‘No support-seekers’ profile had the highest proportions of caregivers who were male, caring for someone \u3c 12 months post-diagnosis and lower income earners. Conclusions: Many rural caregivers seek support for themselves and the cancer patient, commonly from medical and online sources. Implications for public health: Further work may be needed to reduce caregiver burden and support caregivers who are male, caring for someone recently diagnosed, and those with lower incomes

Absolute concentration robustness: Algebra and geometry

Motivated by the question of how biological systems maintain homeostasis in changing environments, Shinar and Feinberg introduced in 2010 the concept of absolute concentration robustness (ACR). A biochemical system exhibits ACR in some species if the steady-state value of that species does not depend on initial conditions. Thus, a system with ACR can maintain a constant level of one species even as the environment changes. Despite a great deal of interest in ACR in recent years, the following basic question remains open: How can we determine quickly whether a given biochemical system has ACR? Although various approaches to this problem have been proposed, we show that they are incomplete. Accordingly, we present new methods for deciding ACR, which harness computational algebra. We illustrate our results on several biochemical signaling networks.Comment: 44 page