The challenges and scope of theoretical biology.

Scientific theories seek to provide simple explanations for significant empirical regularities based on fundamental physical and mechanistic constraints. Biological theories have rarely reached a level of generality and predictive power comparable to physical theories. This discrepancy is explained through a combination of frozen accidents, environmental heterogeneity, and widespread non-linearities observed in adaptive processes.

Proof of concept: pharmacological preconditioning with a Toll-like receptor agonist protects against cerebrovascular injury in a primate model of stroke.

Cerebral ischemic injury is a significant portion of the burden of disease in developed countries; rates of mortality are high and the costs associated with morbidity are enormous. Recent therapeutic approaches have aimed at mitigating the extent of damage and/or promoting repair once injury has occurred. Often, patients at high risk of ischemic injury can be identified in advance and targeted for antecedent neuroprotective therapy.

Electrophysiological evidence for biased competition in V1 for fear expressions.

When multiple stimuli are concurrently displayed in the visual field, they must compete for neural representation at the processing expense of their contemporaries. This biased competition is thought to begin as early as primary visual cortex, and can be driven by salient low-level stimulus features. Stimuli important for an organism's survival, such as facial expressions signaling environmental threat, might be similarly prioritized at this early stage of visual processing.

Regulation of visceral sympathetic tone by A5 noradrenergic neurons in rodents.

The ventrolateral pons contains the A5 group of noradrenergic neurons which regulate the circulation and probably breathing. The present experiments were designed to identify these neurons definitively in vivo, to examine their response to chemoreceptor stimuli (carotid body stimulation and changes in brain pH) and to determine their effects on sympathetic outflow. Bulbospinal A5 neurons, identified by juxtacellular labelling in anaesthetized rats, had a slow regular discharge, were vigorously activated by peripheral chemoreceptor stimulation with cyanide, but only mildly activated by hyperoxic hypercapnia (central chemoreceptor stimulation).

Literate humans sound out words during silent reading.

Whether humans spontaneously sound out words in their mind during silent reading is a matter of debate. Some models of reading postulate that skilled readers access the meaning directly from print but others involve print-to-sound transcoding mechanisms. Here, we provide evidence that silent reading activates the sound form of words before accessing their meaning by comparing event-related potentials induced by highly expected words and their homophones.

Emotion and action: the effect of fear on saccadic performance.

According to evolutionary accounts, emotions originated to prepare an organism for action (Darwin 1872; Frijda 1986). To investigate this putative relationship between emotion and action, we examined the effect of an emotional stimulus on oculomotor actions controlled by the superior colliculus (SC), which has connections with subcortical structures involved in the perceptual prioritization of emotion, such as the amygdala through the pulvinar. The pulvinar connects the amygdala to cells in the SC responsible for the speed of saccade execution, while not affecting the spatial component of the saccade.

Urban scaling and its deviations: revealing the structure of wealth, innovation and crime across cities.

With urban population increasing dramatically worldwide, cities are playing an increasingly critical role in human societies and the sustainability of the planet. An obstacle to effective policy is the lack of meaningful urban metrics based on a quantitative understanding of cities. Typically, linear per capita indicators are used to characterize and rank cities.

Discovery of novel cyclophilin A ligands using an H/D exchange- and mass spectrometry-based strategy.

Cyclophilin A (CypA) is an overexpressed protein in lung cancer tumors and as a result is a potential therapeutic and diagnostic target. Described here is use of an H/D exchange- and a matrix assisted laser desorption/ionization (MALDI) mass spectrometry-based assay, termed single-point SUPREX (Stability of Unpurified Proteins from Rates of H/D Exchange), to screen 2 chemical libraries, including the 1280-compound LOPAC library and the 9600-compound DIVERSet library, for binding to CypA. This work represents the first application of single-point SUPREX using a pooled ligand approach, which is demonstrated here to yield screening rates as fast as 6 s/ligand.

The prevalence of cognitive dysfunction after conventional and computer-assisted total knee replacement.

Post operative cognitive dysfunction (POCD) is common following lower limb arthroplasty. The prevalence varies from 41-75% at 7 days to 18-45% at 3 months post operatively. The wide range of prevalence is due to inconsistencies in defining and quantifying POCD.

Mass spectrometry-based thermal shift assay for protein-ligand binding analysis.

Described here is a mass spectrometry-based screening assay for the detection of protein-ligand binding interactions in multicomponent protein mixtures. The assay utilizes an oxidation labeling protocol that involves using hydrogen peroxide to selectively oxidize methionine residues in proteins in order to probe the solvent accessibility of these residues as a function of temperature. The extent to which methionine residues in a protein are oxidized after specified reaction times at a range of temperatures is determined in a MALDI analysis of the intact proteins and/or an LC-MS analysis of tryptic peptide fragments generated after the oxidation reaction is quenched.

Red diffuse light suppresses the accelerated perception of fear.

Prioritization of affective events may occur via two parallel pathways originating from the retina-a parvocellular (P) pathway projecting to ventral-stream structures responsible for object recognition or a faster and phylogenetically older magnocellular (M) pathway projecting to dorsal-stream structures responsible for localization and action. It has previously been demonstrated that retinal exposure to red diffuse light suppresses M-cell neural activity. We tested whether the fast propagation along the dorsal-action pathway drives an accelerated conduction of fear-based content.

Capacity limits during perceptual encoding.

When a unique stimulus is embedded in an otherwise homogenous display, it is thought to "pop-out" due to its relative increase in salience. We investigated whether the visual system has the ability to equally prioritize multiple salient pop-out items competing for awareness or whether this early stage of visual processing is constrained by capacity limits. We used signal detection (d') methods to determine if sensitivity to a salient pop-out item decreases as function of the number of total salient items present in the visual display.

Quantitative proteomics approach for identifying protein-drug interactions in complex mixtures using protein stability measurements.

Knowledge about the protein targets of therapeutic agents is critical for understanding drug mode of action. Described here is a mass spectrometry-based proteomics method for identifying the protein target(s) of drug molecules that is potentially applicable to any drug compound. The method, which involves making thermodynamic measurements of protein-folding reactions in complex biological mixtures to detect protein-drug interactions, is demonstrated in an experiment to identify yeast protein targets of the immunosuppressive drug, cyclosporin A (CsA).

In vitro fertilization and sperm cryopreservation in the black-footed cat (Felis nigripes) and sand cat (Felis margarita).

Studies of in vitro fertilization (IVF) and sperm cryopreservation have been conducted in several small cat species, but virtually no data exist for black-footed cats (Felis nigripes) (BFCs) or sand cats (Felis margarita) (SCs). The objectives of this study were 1) to compare in vitro motility and acrosome status of fresh and cryopreserved (frozen in pellets on dry ice or in straws in liquid nitrogen vapor) BFC and SC spermatozoa cultured in feline-optimized culture medium (FOCM) or Ham F-10, 2) to assess ovarian responsiveness in BFCs and SCs following exogenous gonadotropin treatment and laparoscopic oocyte recovery, and 3) to evaluate the fertility of fresh and frozen-thawed spermatozoa from both species using homologous and heterologous (domestic cat oocytes) IVF in the two culture media. Motility and acrosomal integrity of fresh and frozen-thawed spermatozoa from BFCs and SCs were similar (P > 0.

Dural augmentation: part I-evaluation of collagen matrix allografts for dural defect after craniotomy.

Objective: Primary closure of the dura remains difficult in many neurosurgical cases. One option for dural grafting is the collagen sponge, which is available in multiple forms, namely, monolayer collagen and bilayer collagen. Our primary goal was to assess differences in the incidence of postoperative cerebrospinal fluid (CSF) leak, including fistula and pseudomeningocele, and postoperative infection between monolayer collagen and bilayer collagen grafts.

Photostimulation of channelrhodopsin-2 expressing ventrolateral medullary neurons increases sympathetic nerve activity and blood pressure in rats.

To explore the specific contribution of the C1 neurons to blood pressure (BP) control, we used an optogenetic approach to activate these cells in vivo. A lentivirus that expresses channelrhodopsin-2 (ChR2) under the control of the catecholaminergic neuron-preferring promoter PRSx8 was introduced into the rostral ventrolateral medulla (RVLM). After 2-3 weeks, ChR2 was largely confined to Phox2b-expressing neurons (89%).

Activation of the retrotrapezoid nucleus by posterior hypothalamic stimulation.

The retrotrapezoid nucleus (RTN) contains chemically defined neurons (ccRTN neurons) that provide a pH-regulated excitatory drive to the central respiratory pattern generator. Here we test whether ccRTN neurons respond to stimulation of the perifornical hypothalamus (PeF), a region that regulates breathing during sleep, stress and exercise. PeF stimulation with gabazine increased blood pressure, phrenic nerve discharge (PND) and the firing rate of ccRTN neurons in isoflurane-anaesthetized rats.

Acid sensitivity and ultrastructure of the retrotrapezoid nucleus in Phox2b-EGFP transgenic mice.

The retrotrapezoid nucleus (RTN) contains noncholinergic noncatecholaminergic glutamatergic neurons that express the transcription factor Phox2b (chemically coded or "cc" RTN neurons). These cells regulate breathing and may be central chemoreceptors. Here we explore their ultrastructure and their acid sensitivity by using two novel BAC eGFP-Phox2b transgenic mice (B/G, GENSAT JX99) in which, respectively, 36% and 100% of the cc RTN neurons express the transgene in complete or partial anatomical isolation from other populations of eGFP neurons.

Motivationally significant stimuli show visual prior entry: evidence for attentional capture.

Previous studies that have found attentional capture effects for stimuli of motivational significance do not directly measure initial attentional deployment, leaving it unclear to what extent these items produce attentional capture. Visual prior entry, as measured by temporal order judgments (TOJs), rests on the premise that allocated attention accelerates perception, that is, stimuli that receive attention first are perceived first; thus, this method is a sensitive and direct measure of the time course of initial attentional deployment. The authors demonstrate, using a novel TOJ paradigm without cues, that displays of faces and facial threat show visual prior entry effects, that is, these stimuli are prioritized by the perceptual-attentional system over other stimuli competing for awareness.

Shock-synthesized hexagonal diamonds in Younger Dryas boundary sediments.

The long-standing controversy regarding the late Pleistocene megafaunal extinctions in North America has been invigorated by a hypothesis implicating a cosmic impact at the Allerød-Younger Dryas boundary or YDB (approximately 12,900 +/- 100 cal BP or 10,900 +/- 100 (14)C years). Abrupt ecosystem disruption caused by this event may have triggered the megafaunal extinctions, along with reductions in other animal populations, including humans. The hypothesis remains controversial due to absence of shocked minerals, tektites, and impact craters.

The protein-tyrosine phosphatase, SRC homology-2 domain containing protein tyrosine phosphatase-2, is a crucial mediator of exogenous insulin-like growth factor signaling to human trophoblast.

Adequate fetal growth depends on placental transfer of nutrients and gases from the mother; thus, as pregnancy progresses, the placenta must grow to meet the increasing demands of the developing fetus. IGFs control proliferation, differentiation, and survival of trophoblast in first-trimester placenta via intracellular tyrosine kinase signaling cascades, the activation of which is also regulated by tyrosine phosphatases. The protein-tyrosine phosphatase, Src homology-2 domain containing protein tyrosine phosphatase (SHP)-2, is crucial for mouse placental development and is known to mediate IGF actions in other systems.

Fecal endocrine profiles and ejaculate traits in black-footed cats (Felis nigripes) and sand cats (Felis margarita).

Information regarding the reproductive biology of black-footed cats (BFC) and sand cats (SC) is extremely limited. Our objectives were to: (1) validate fecal hormone analysis (estrogens, E; progestagens, P; androgens, T) for noninvasive monitoring of gonadal activity; (2) characterize estrous cyclicity, ovulatory mechanisms, gestation, and seasonality; and (3) evaluate male reproductive activity via fecal androgen metabolites and ejaculate traits. In both species, the estrous cycle averaged 11-12 days.

Dining experience, foodservices and staffing are associated with quality of life in elderly nursing home residents.

Purpose: Few studies have quantitatively investigated potential relationships between quality of life (QOL) in long term care (LTC) and foodservices.

Objective: To investigate if dining experiences, and food and nutritional services affect elderly nursing home residents' QOL.

Design And Participants: A total of 395 residents in 38 nursing homes participated in this cross-sectional study.

Photostimulation of retrotrapezoid nucleus phox2b-expressing neurons in vivo produces long-lasting activation of breathing in rats.

The retrotrapezoid "nucleus" (RTN), located in the rostral ventrolateral medullary reticular formation, contains a bilateral cluster of approximately 1000 glutamatergic noncatecholaminergic Phox2b-expressing propriobulbar neurons that are activated by CO(2) in vivo and by acidification in vitro. These cells are thought to function as central respiratory chemoreceptors, but this theory still lacks a crucial piece of evidence, namely that stimulating these particular neurons selectively in vivo increases breathing. The present study performed in anesthetized rats seeks to test whether this expectation is correct.