Hot off the presses! Apr 26 curr biol

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Latest Articles Include:

• Revived interest in bacteriophages
  - curr biol 21(8):R267-R270 (2011)
  Phages have a track record of being left behind whenever science moves on to other things. But will the inexorable spread of antibiotic resistance lead to a revival of their role as antibacterial therapeutics? Michael Gross investigates.
• Nancy Knowlton
  - curr biol 21(8):R270-R271 (2011)
  
• Strepsiptera
  - curr biol 21(8):R271-R272 (2011)
  
• Animal Eyes: Defending the Coat of Mail
  - curr biol 21(8):R273-R274 (2011)
  The eyes on the backs of molluscs known as chitons are shadow and motion detectors, the lenses of which are made of birefringent aragonite. These provide a focus both in and out of water.
• Developmental Biology: Small RNAs Play Their Part
  - curr biol 21(8):R274-R276 (2011)
  What mechanisms coordinate the sequential pattern of gene expression during development of specialized cells? A small RNA-based mechanism is proposed to repress expression of genes during oogenesis.
• Neural Networks: More about Flexibility Than Synaptic Strength
  - curr biol 21(8):R276-R278 (2011)
  The leech heartbeat neural network is famous for its constancy in both architecture and functional output across animals. A recent study, however, has found that the synaptic strengths underlying this constancy are quite variable across animals.
• Animal Communication: Flies' Ears Are Tuned In
  - curr biol 21(8):R278-R280 (2011)
  Male fruit flies sing to females with quiet, close-range wing vibrations. A new study has found that the flies' antennal ears show active tuning to the species-specific frequencies of songs.
• Invadopodia: RhoC Runs Rings around Cofilin
  - curr biol 21(8):R280-R282 (2011)
  Tumor cell invadopodia mediate degradation of matrix barriers. A new study now demonstrates that a ring of active RhoC focuses invadopodial protrusion and degradation by regulating cofilin activity.
• Cognitive Neuroscience: Feedback for Natural Visual Stimuli
  - curr biol 21(8):R282-R283 (2011)
  Recurrent signals in the brain are often associated with slower sensory and cognitive processes. Such patterns of activity may also form the basis of rapid perception.
• Microtubule End Binding: EBs Sense the Guanine Nucleotide State
  - curr biol 21(8):R283-R285 (2011)
  EB proteins accumulate at the tips of growing microtubules and recruit to them a multitude of factors to regulate microtubule functions. A new study suggests that EBs recognize microtubule ends by distinguishing between different states of the tubulin-bound guanine nucleotide.
• Alternative Strategies: The Evolution of Switch Points
  - curr biol 21(8):R285-R287 (2011)
  The evolution of conditional, alternative strategies is a major factor in adaptation. In animals, the frequency of alternative morphs, characterized by different morphologies and mating tactics, can be both condition-dependent and subject to rapid evolutionary change.
• Motor Learning: Spare the Rod to Benefit the Child?
  - curr biol 21(8):R287-R288 (2011)
  A new study has found that individuals who were rewarded while they learned a motor task performed it much better one month later than those who were punished or received nothing. Long-term memories depend on events experienced during learning.
• Oogenesis: When Most Is Good Enough
  - curr biol 21(8):R288-R290 (2011)
  In male meiosis an unaligned chromosome blocks meiotic progression. However, oocytes with one or more misaligned chromosomes can complete meiosis. This difference reflects a more permissive role of the spindle assembly checkpoint, rather than solely reflecting the ability of some univalents to adopt a meiosis II-like orientation on the spindle.
• Glial Cells Physiologically Modulate Clock Neurons and Circadian Behavior in a Calcium-Dependent Manner
  - curr biol 21(8):625-634 (2011)
  Background An important goal of contemporary neuroscience research is to define the neural circuits and synaptic interactions that mediate behavior. In both mammals and Drosophila, the neuronal circuitry controlling circadian behavior has been the subject of intensive investigation, but roles for glial cells in the networks controlling rhythmic behavior have only begun to be defined in recent studies. Results Here, we show that conditional, glial-specific genetic manipulations affecting membrane (vesicle) trafficking, the membrane ionic gradient, or calcium signaling lead to circadian arrhythmicity in adult behaving Drosophila. Correlated and reversible effects on a clock neuron peptide transmitter (PDF) and behavior demonstrate the capacity for glia-to-neuron signaling in the circadian circuitry. These studies also reveal the importance of a single type of glial cell—the astrocyte—and glial internal calcium stores in the regulation of circadian rhythms. Conclusions This is the first demonstration in any system that adult glial cells can physiologically modulate circadian neuronal circuitry and behavior. A role for astrocytes and glial calcium signaling in the regulation of Drosophila circadian rhythms emphasizes the conservation of cellular and molecular mechanisms that regulate behavior in mammals and insects.
• A Novel Spatiotemporal RhoC Activation Pathway Locally Regulates Cofilin Activity at Invadopodia
  - curr biol 21(8):635-644 (2011)
  Background RhoGTPases have been implicated in the regulation of cancer metastasis. Invasive carcinoma cells form invadopodia, F-actin-rich matrix-degrading protrusions that are thought to be important for tumor cell invasion and intravasation. Regulation of actin dynamics at invadopodial protrusions is crucial to drive invasion. This process requires the severing activity of cofilin to generate actin-free barbed ends. Previous work demonstrates that cofilin's severing activity is tightly regulated through multiple mechanisms, including regulation of cofilin serine phosphorylation by Rho GTPases. However, it is not known which Rho GTPase is involved in regulating cofilin's phosphorylation status at invadopodia. Results We show here, for the first time, how RhoC activation is controlled at invadopodia and how this activation regulates cofilin phosphorylation to control cofilin's generation of actin-free barbed ends. Live-cell imaging of fluorescent RhoC biosensor reveals that RhoC activity is spatially confined to areas surrounding invadopodia. This spatiotemporal restriction of RhoC activity is controlled by "spatially distinct regulatory elements" that confine RhoC activation within this compartment. p190RhoGEF localizes around invadopodia to activate RhoC, whereas p190RhoGAP localizes inside invadopodia to deactivate the GTPase within the structure. RhoC activation enhances cofilin phosphorylation outside invadopodia. Conclusion These results show how RhoC activity is spatially regulated at invadopodia by p190RhoGEF and p190RhoGAP. RhoC activation in areas surrounding invadopodia restricts cofilin activity to within the invadopodium core, resulting in a focused invadopodial protrusion. This mechanism likely enhances tumor cell invasion during metastasis.
• A Common Frame of Reference for Learned and Communicated Vectors in Honeybee Navigation
  - curr biol 21(8):645-650 (2011)
  Humans draw maps when communicating about places or verbally describe routes between locations. Honeybees communicate places by encoding distance and direction in their waggle dances [1]. Controversy exists not only about the structure of spatial memory but also about the efficiency of dance communication [[2], [3], [4] and [5]]. Some of these uncertainties were resolved by studies in which recruits' flights were monitored using harmonic radar [[6] and [7]]. We asked whether the two sources of vector information—the previously learned flight vector to a food source and the communicated vector—are represented in a common frame of spatial reference. We found that recruits redirect their outbound flights and perform novel shortcut flights between the communicated and learned locations in both directions. Guidance by beacons at the respective locations or by the panorama of the horizon was excluded. These findings indicate a spatial reference based on either large-scal! e vector integration or a common geocentric map-like spatial memory. Both models predict a memory structure that stores the spatial layout in such a way that decisions are made according to estimated distances and directions. The models differ with respect to the role of landmarks and the time of learning of spatial relations.
• Oocyte-Specific Differences in Cell-Cycle Control Create an Innate Susceptibility to Meiotic Errors
  - curr biol 21(8):651-657 (2011)
  Segregation of homologs at the first meiotic division (MI) is facilitated by crossovers and by a physical constraint imposed on sister kinetochores that facilitates monopolar attachment to the MI spindle. Recombination failure or premature separation of homologs results in univalent chromosomes at MI, and univalents constrained to form monopolar attachments should be inherently unstable and trigger the spindle assembly checkpoint (SAC) [1]. Although univalents trigger cell-cycle arrest in the male [[2], [3], [4] and [5]], this is not the case in mammalian oocytes [[6] and [7]]. Because the spindle assembly portion of the SAC appears to function normally [[8], [9] and [10]], two hypotheses have been proposed to explain the lack of response to univalents: (1) reduced stringency of the oocyte SAC to aberrant chromosome behavior [7], and (2) the ability of univalents to satisfy the SAC by forming bipolar attachments [6]. The present study of Mlh1 mutant mice demonstrates t! hat metaphase alignment is not a prerequisite for anaphase onset and provides strong evidence that MI spindle stabilization and anaphase onset require stable bipolar attachment of a critical mass—but not all—of chromosomes. We postulate that subtle differences in SAC-mediated control make the human oocyte inherently error prone and contribute to the age-related increase in aneuploidy.
• Active Process Mediates Species-Specific Tuning of Drosophila Ears
  - curr biol 21(8):658-664 (2011)
  The courtship behavior of Drosophilid flies has served as a long-standing model for studying the bases of animal communication [1]. During courtship, male flies flap their wings to send a complex pattern of airborne vibrations to the antennal ears of the females. These "courtship songs" differ in their spectrotemporal composition across species and are considered a crucial component of the flies' premating barrier [[2] and [3]]. However, whether the species-specific differences in song structure are also reflected in the receivers of this communication system, i.e., the flies' antennal ears, has remained unexplored. Here we show for seven members of the melanogaster species group that (1) their ears are mechanically tuned to different best frequencies, (2) the ears' best frequencies correlate with high-frequency pulses of the conspecific courtship songs, and (3) the species-specific tuning relies on amplificatory mechanical feedback from the flies' auditory neurons! . As a result of its level-dependent nature [[4] and [5]], the active mechanical feedback amplification is particularly useful for the detection of small stimuli, such as conspecific song pulses, and becomes negligible for sensing larger stimuli, such as the flies' own wingbeat during flight.
• A Chiton Uses Aragonite Lenses to Form Images
  - curr biol 21(8):665-670 (2011)
  Hundreds of ocelli are embedded in the dorsal shell plates of certain chitons [1]. These ocelli each contain a pigment layer, retina, and lens [2], but it is unknown whether they provide chitons with spatial vision [3]. It is also unclear whether chiton lenses are made from proteins, like nearly all biological lenses, or from some other material [4]. Electron probe X-ray microanalysis and X-ray diffraction revealed that the chiton Acanthopleura granulata has the first aragonite lenses ever discovered. We found that these lenses allow A. granulata's ocelli to function as small camera eyes with an angular resolution of about 9°–12°. Animals responded to the sudden appearance of black, overhead circles with an angular size of 9°, but not to equivalent, uniform decreases in the downwelling irradiance. Our behavioral estimates of angular resolution were consistent with estimates derived from focal length and receptor spacing within the A. granulata eye. Behavioral tria! ls further indicated that A. granulata's eyes provide the same angular resolution in both air and water. We propose that one of the two refractive indices of the birefringent chiton lens places a focused image on the retina in air, whereas the other does so in water.
• Evolutionary Convergence on Sleep Loss in Cavefish Populations
  - curr biol 21(8):671-676 (2011)
  Patterns of sleep vary widely among species [[1], [2], [3] and [4]], but the functional and evolutionary principles responsible for this diversity remain unknown. The characin fish, Astyanax mexicanus, has eyed surface and numerous blind cave populations [5]. The cave populations are largely independent in their origins, and the species is ideal for studying the genetic bases of convergent evolution [[5], [6] and [7]]. Here we show that this system is also uniquely valuable for the investigation of variability in patterns of sleep. We find that a clearly defined change in ecological conditions, from surface to cave, is correlated with a dramatic reduction in sleep in three independently derived cave populations of A. mexicanus. Analyses of surface × cave hybrids show that the alleles for reduced sleep in the Pachón and Tinaja cave populations are dominant in effect to the surface alleles. Genetic analysis of hybrids between surface and Pachón cavefish suggests that ! only a small number of loci with dominant effects are involved. Our results demonstrate that sleep is an evolutionarily labile phenotype, highly responsive to changes in ecological conditions. To our knowledge, this is the first example of a single species with a convergence on sleep loss exhibited by several independently evolved populations correlated with population-specific ecologies.
• Political Orientations Are Correlated with Brain Structure in Young Adults
  - curr biol 21(8):677-680 (2011)
  Substantial differences exist in the cognitive styles of liberals and conservatives on psychological measures [1]. Variability in political attitudes reflects genetic influences and their interaction with environmental factors [[2] and [3]]. Recent work has shown a correlation between liberalism and conflict-related activity measured by event-related potentials originating in the anterior cingulate cortex [4]. Here we show that this functional correlate of political attitudes has a counterpart in brain structure. In a large sample of young adults, we related self-reported political attitudes to gray matter volume using structural MRI. We found that greater liberalism was associated with increased gray matter volume in the anterior cingulate cortex, whereas greater conservatism was associated with increased volume of the right amygdala. These results were replicated in an independent sample of additional participants. Our findings extend previous observations that polit! ical attitudes reflect differences in self-regulatory conflict monitoring [4] and recognition of emotional faces [5] by showing that such attitudes are reflected in human brain structure. Although our data do not determine whether these regions play a causal role in the formation of political attitudes, they converge with previous work [[4] and [6]] to suggest a possible link between brain structure and psychological mechanisms that mediate political attitudes.
• Caveolin-1 Deficiency Causes Cholesterol-Dependent Mitochondrial Dysfunction and Apoptotic Susceptibility
  - curr biol 21(8):681-686 (2011)
  Caveolins (CAVs) are essential components of caveolae, plasma membrane invaginations with reduced fluidity, reflecting cholesterol accumulation [1]. CAV proteins bind cholesterol, and CAV's ability to move between cellular compartments helps control intracellular cholesterol fluxes [[1], [2] and [3]]. In humans, CAV1 mutations result in lipodystrophy, cell transformation, and cancer [[4], [5], [6] and [7]]. CAV1 gene-disrupted mice exhibit cardiovascular diseases, diabetes, cancer, atherosclerosis, and pulmonary fibrosis [[8] and [9]]. The mechanism or mechanisms underlying these disparate effects are unknown, but our past work suggested that CAV1 deficiency might alter metabolism: CAV1−/− mice exhibit impaired liver regeneration unless supplemented with glucose, suggesting systemic inefficiencies requiring additional metabolic intermediates [10]. Establishing a functional link between CAV1 and metabolism would provide a unifying theme to explain these myriad patho! logies [11]. Here we demonstrate that impaired proliferation and low survival with glucose restriction is a shortcoming of CAV1-deficient cells caused by impaired mitochondrial function. Without CAV1, free cholesterol accumulates in mitochondrial membranes, increasing membrane condensation and reducing efficiency of the respiratory chain and intrinsic antioxidant defense. Upon activation of oxidative phosphorylation, this promotes accumulation of reactive oxygen species, resulting in cell death. We confirm that this mitochondrial dysfunction predisposes CAV1-deficient animals to mitochondrial-related diseases such as steatohepatitis and neurodegeneration.
• Dynamic Horizontal Cultural Transmission of Humpback Whale Song at the Ocean Basin Scale
  - curr biol 21(8):687-691 (2011)
  Cultural transmission, the social learning of information or behaviors from conspecifics [[1], [2], [3], [4] and [5]], is believed to occur in a number of groups of animals, including primates [[1], [6], [7], [8] and [9]], cetaceans [[4], [10] and [11]], and birds [[3], [12] and [13]]. Cultural traits can be passed vertically (from parents to offspring), obliquely (from the previous generation via a nonparent model to younger individuals), or horizontally (between unrelated individuals from similar age classes or within generations) [4]. Male humpback whales (Megaptera novaeangliae) have a highly stereotyped, repetitive, and progressively evolving vocal sexual display or "song" [[14], [15], [16] and [17]] that functions in sexual selection (through mate attraction and/or male social sorting) [[18], [19] and [20]]. All males within a population conform to the current version of the display (song type), and similarities may exist among the songs of populations within! an ocean basin [[16], [17] and [21]]. Here we present a striking pattern of horizontal transmission: multiple song types spread rapidly and repeatedly in a unidirectional manner, like cultural ripples, eastward through the populations in the western and central South Pacific over an 11-year period. This is the first documentation of a repeated, dynamic cultural change occurring across multiple populations at such a large geographic scale.
• Geminin Escapes Degradation in G1 of Mouse Pluripotent Cells and Mediates the Expression of Oct4, Sox2, and Nanog
  - curr biol 21(8):692-699 (2011)
  Geminin is an essential cell-cycle protein that is only present from S phase to early mitosis in metazoan somatic cells [[1] and [2]]. Genetic ablation of geminin in the mouse results in preimplantation embryonic lethality because pluripotent cells fail to form and all cells differentiate to trophoblast [[3] and [4]]. Here we show that geminin is present in G1 phase of mouse pluripotent cells in contrast to somatic cells, where anaphase-promoting complex/cyclosome (APC/C)-mediated proteasomal destruction removes geminin in G1 [[1], [2] and [5]]. Silencing geminin directly or by depleting the APC/C inhibitor Emi1 causes loss of stem cell identity and trophoblast differentiation of mouse embryonal carcinoma and embryonic stem cells. Depletion of cyclins A2 or B1 does not induce this effect, even though both of these APC/C substrates are also present during G1 of pluripotent cells. Crucially, geminin antagonizes the chromatin-remodeling protein Brg1 to maintain expression! of Oct4, Sox2, and Nanog. Our results define a pluripotency pathway by which suppressed APC/C activity protects geminin from degradation in G1, allowing sustained expression of core pluripotency factors. Collectively, these findings link the cell cycle to the pluripotent state but also raise an unexplained paradox: How is cell-cycle progression possible in pluripotent cells when oscillations of key regulatory proteins are lost?
• Gene Duplication in Mimulus Underlies Parallel Floral Evolution via Independent trans-Regulatory Changes
  - curr biol 21(8):700-704 (2011)
  Identifying the genetic basis of parallelism reveals the means by which evolution repeats itself and shows what aspects—if any—may be predictable [1]. The recently tetraploid luteus group of Mimulus [2] contains five species native to central Chile [3], three of which have evolved extensive red floral pigmentation using at least two distinct loci [4]. Here we show that the parallel evolution of petal lobe anthocyanin (PLA) pigmentation in M. cupreus and M. luteus var. variegatus occurred via separate yet strikingly similar mechanisms. In each case, a dominant, single-locus gain of pigmentation [4] maps to a genomic region (pla1 and pla2, respectively) containing adjacent, apparently recently duplicated paralogs of MYB anthocyanin-regulating transcription factors. Interestingly, candidate genes in pla1 and pla2 are themselves related by an older duplication. In both cases, pla genotype cosegregates with expression of multiple genes in the anthocyanin biosynthetic pa! thway, revealing a mechanism of coordinated trans-regulatory expression changes across functionally related enzyme-encoding genes. We conclude that in this instance, evolution has repeated itself with marked consistency. Duplication has enabled that repetition to occur using two physically independent but functionally similar loci, highlighting the importance of genomic complexity to the evolutionary process.
• KIBRA Suppresses Apical Exocytosis through Inhibition of aPKC Kinase Activity in Epithelial Cells
  - curr biol 21(8):705-711 (2011)
  Epithelial cells possess apical-basolateral polarity and form tight junctions (TJs) at the apical-lateral border, separating apical and basolateral membrane domains. The PAR3-aPKC-PAR6 complex plays a central role in TJ formation and apical domain development during tissue morphogenesis [[1], [2], [3] and [4]]. Inactivation and overactivation of aPKC kinase activity disrupts membrane polarity [[5], [6], [7] and [8]]. The mechanism that suppresses active aPKC is unknown. KIBRA, an upstream regulator of the Hippo pathway, regulates tissue size in Drosophila [[9], [10] and [11]] and can bind to aPKC [[12] and [13]]. However, the relationship between KIBRA and the PAR3-aPKC-PAR6 complex remains unknown. We report that KIBRA binds to the PAR3-aPKC-PAR6 complex and localizes at TJs and apical domains in epithelial tissues and cells. The knockdown of KIBRA causes expansion of the apical domain in MDCK three-dimensional cysts and suppresses the formation of apical-containing v! acuoles through enhanced de novo apical exocytosis. These phenotypes are restored by inhibition of aPKC. In addition, KIBRA directly inhibits the kinase activity of aPKC in vitro. These results strongly support the notion that KIBRA regulates epithelial cell polarity by suppressing apical exocytosis through direct inhibition of aPKC kinase activity in the PAR3-aPKC-PAR6 complex.
• Suppression of Ptf1a Activity Induces Acinar-to-Endocrine Conversion
  - curr biol 21(8):712-717 (2011)
  Pluripotent embryonic cells become progressively lineage restricted during development in a process that culminates in the differentiation of stable organ-specific cell types that perform specialized functions. Terminally differentiated pancreatic acinar cells do not have the innate capacity to contribute to the endocrine β cell lineage, which is destroyed in individuals with autoimmune diabetes [1]. Some cell types can be reprogrammed using a single factor [[2] and [3]], whereas other cell types require continuous activity of transcriptional regulators to repress alternate cell fates [[4], [5] and [6]]. Thus, we hypothesized that a transcriptional network continuously maintains the pancreatic acinar cell fate. We found that postembryonic antagonism of Ptf1a, a master regulator of pancreatic development [7] and acinar cell fate specification [[8] and [9]], induced the expression of endocrine genes including insulin in the exocrine compartment. Using a genetic lineage ! tracing approach, we show that the induced insulin+ cells are derived from acinar cells. Cellular reprogramming occurred under homeostatic conditions, suggesting that the pancreatic microenvironment is sufficient to promote endocrine differentiation. Thus, severe experimental manipulations [[10] and [11]] may not be required to potentiate pancreatic transdifferentiation. These data indicate that targeted postembryonic disruption of the acinar cell fate can restore the developmental plasticity that is lost during development.