A Blog Around The Clock

As always on Monday night, there are new articles published in PLoS Biology and PLoS Medicine. Here are some of the highlights:

Shedding Light on Animal Cryptochromes:

Anyone who’s neglected a houseplant for any length of time knows that plants can’t survive without light. But it’s more complicated than that; in addition to serving as an energy source, light is used by plants as a signal to sense and respond to the environment. For example, both red and blue light send the signal for maturation and flower and seed development. Depriving a plant of such light signals disrupts a variety of growth processes such as early seedling development, leaf and stem expansion, and initiation of flowering, as well as circadian clock entrainment. Cryptochromes are photoreceptor proteins used by plants to mediate the effects of blue light; they are also found in animals like flies and mice, where they help to regulate the circadian clock. In plants, exposure to blue light results in the reduction (gain of electrons) of flavin pigments that are bound by the cryptochrome. Blue light activates plant cryptochromes by reducing the flavins, but researchers weren’t sure exactly how blue light activates fly cryptochromes, or if mammalian cryptochromes even respond to light at all.

Human and Drosophila Cryptochromes Are Light Activated by Flavin Photoreduction in Living Cells:

Vision in animals is generally associated with light-sensitive rhodopsin pigments located in the eyes. However, animals ranging from flies to humans also possess ancient visual receptors known as cryptochromes in multiple cell types. In this work, we study the mechanism of light sensing in two representative animal cryptochromes: a light-sensitive Drosophila cryptochrome (Dmcry) and a presumed light-insensitive mammalian cryptochrome from humans (Hscry1). We expressed recombinant cryptochromes to high levels in living cells, irradiated the cells with blue light, and analyzed the proteins’ response to irradiation with electron paramagnetic resonance and fluorescence spectroscopic techniques. Photoreduction of protein-bound oxidized FAD cofactor to its radical form emerged as the primary cryptochrome photoreaction in living cells, and was correlated with a light-sensitive biological response in whole organisms. These results indicate that both Dmcry and Hscry1 are capable of undergoing similar light-driven reactions and suggest the possibility of an as-yet unknown photo-perception role for human cryptochromes in tissues exposed to light.

From Structure to Function: Mapping the Connection Matrix of the Human Brain:

When American architect Louis Sullivan proffered the enduring mantra of 20th century design–form follows function–he chided his peers for violating in art a law so clearly visible in the “open apple blossom” and “sweeping eagle in his flight.” The notion that the essence of things takes shape in the matter of things, first articulated in Aristotle’s philosophy, has long guided biologists’ attempts to understand the inner workings of the most complex organ known–the human brain. Fine-grained descriptions of anatomical features of the eye and ear, for example, have yielded critical insights into the neural basis of image and sound perception. But for a systems-level understanding of how the brain works, researchers look to the overall topology of network connections among neurons for answers.

Neuronal Correlates of the Set-Size Effect in Monkey Lateral Intraparietal Area:

It is well known that the brain is limited in the amount of sensory information that it can process at any given time. During an everyday task such as finding an object in a cluttered environment (known as visual search), observers take longer to find a target as the number of distractors increases. This well-known phenomenon implies that inputs from distractors interfere with the brain’s ability to perceive the target at some stage or stages of neural processing. However, the loci and mechanisms of this interference are unknown. Visual information is processed in feature-selective areas that encode the physical properties of stimuli and in higher-order areas that convey information about behavioral significance and help direct attention to individual stimuli. Here we studied a higher-order parietal area related to attention and eye movements. We found that parietal neurons selectively track the location of a search target during a difficult visual search task. However, neuronal firing rates decreased as distractors were added to the display, and the decrease in the target-related response correlated with the set-size-related increase in reaction time. This suggests that distractors trigger competitive visuo-visual interactions that limit the brain’s ability to find and focus on a task-relevant target.

Mapping the Structural Core of Human Cerebral Cortex:

In the human brain, neural activation patterns are shaped by the underlying structural connections that form a dense network of fiber pathways linking all regions of the cerebral cortex. Using diffusion imaging techniques, which allow the noninvasive mapping of fiber pathways, we constructed connection maps covering the entire cortical surface. Computational analyses of the resulting complex brain network reveal regions of cortex that are highly connected and highly central, forming a structural core of the human brain. Key components of the core are portions of posterior medial cortex that are known to be highly activated at rest, when the brain is not engaged in a cognitively demanding task. Because we were interested in how brain structure relates to brain function, we also recorded brain activation patterns from the same participant group. We found that structural connection patterns and functional interactions between regions of cortex were significantly correlated. Based on our findings, we suggest that the structural core of the brain may have a central role in integrating information across functionally segregated brain regions.

Toward a Global View of Alcohol, Tobacco, Cannabis, and Cocaine Use: Findings from the WHO World Mental Health Surveys:

Alcohol, tobacco, and illegal drug use are held responsible for considerable mortality and morbidity [1], but in the most recent World Health Organization (WHO) Global Burden of Disease estimates, the authors unanimously asserted that better epidemiological data on use were needed, particularly in less established market economies [2-4]. This paper presents data on lifetime alcohol, tobacco, cannabis, and cocaine use from rigorously conducted field surveys using a common research approach in the first 17 countries to participate in the WHO’s World Mental Health (WMH) Survey Initiative [5,6]. A number of less established market economies are included in this set of countries.

Documenting Mortality in Crises: What Keeps Us from Doing Better?:

The effects of crises (man-made or natural disasters) on physical health are ultimately quantifiable as a rise in mortality. Precise and unbiased estimates of mortality rates (deaths per person-time) or excess death tolls (deaths attributable to the presence of the crisis) are critical to grading the severity of a crisis at its onset and over time, and adjusting relief operations accordingly [1,2]. Indeed, the onset of emergencies is commonly defined as a doubling of mortality rate from the pre-crisis baseline, or the crossing of fixed thresholds, typically one death per 10,000 person-days [2]. In reality, because mortality increases only after a crisis has evolved, acute malnutrition may be a better indicator for early crisis detection [3], and data on morbidity and on the coverage of interventions against the main known risk factors for poor health outcomes (e.g., insufficient water and sanitation, lack of preventive and curative health services, etc.) are more useful to target relief programmes and minimise preventable deaths.