Recent reports of the lack of periodic orientation columns in a very large rodent species, the red-rumped agouti, and the existence of incompressible hypercolumns in the lineage of primates, as ...demonstrated in one of the smallest primates, the mouse lemur, strengthen the interpretation that salt-and-pepper and columns-and-pinwheel mosaics are two distinct functional layouts. These layouts do neither depend on lifestyle nor scale with body size, brain size, absolute neuron numbers, binocular overlap, or visual acuity, but are primarily distinguishable by phylogenetic traits. The predictive value of other biological signatures such as V1 neuronal surface density and the central-peripheral density ratio of retinal ganglion cells are reconsidered, and experiments elucidating the intracortical connectivity in rodents are proposed.
•Informed taxon sampling elucidates the dependence of V1 functional architecture on lifestyle, brain size, and lineage.•Orientation-selective neurons appear in one of two categorially distinct layouts, columns-and-pinwheels or salt-and-pepper.•In mammalian V1, salt-and-pepper is the most likely ancestral condition.•In support of a punctuated equilibrium mode for V1 circuits, both layouts exhibit minimal intra-lineage differences.•Circuit level theories associate salt-and-pepper with random and columns-and-pinwheels with orientation-selective wiring.
Cilia formation is a multi-step process that starts with the docking of a vesicle at the distal part of the mother centriole. This step marks the conversion of the mother centriole into the basal ...body, from which axonemal microtubules extend to form the ciliary compartment. How vesicles are stably attached to the mother centriole to initiate ciliary membrane biogenesis is unknown. Here, we investigate the molecular role of the mother centriolar component Cep164 in ciliogenesis. We show that Cep164 was indispensable for the docking of vesicles at the mother centriole. Using biochemical and functional assays, we identified the components of the vesicular transport machinery, the GEF Rabin8 and the GTPase Rab8, as interacting partners of Cep164. We propose that Cep164 is targeted to the apical domain of the mother centriole to provide the molecular link between the mother centriole and the membrane biogenesis machinery that initiates cilia formation.
How cells coordinate their metabolism with division determines the rate of cell proliferation. Dynamic patterns of metabolite synthesis during the cell cycle are unexplored. We report the first ...isotope tracing analysis in synchronous, growing budding yeast cells. Synthesis of leucine, a branched-chain amino acid (BCAA), increases through the G1 phase of the cell cycle, peaking later during DNA replication. Cells lacking Bat1, a mitochondrial aminotransferase that synthesizes BCAAs, grow slower, are smaller, and are delayed in the G1 phase, phenocopying cells in which the growth-promoting kinase complex TORC1 is moderately inhibited. Loss of Bat1 lowers the levels of BCAAs and reduces TORC1 activity. Exogenous provision of valine and, to a lesser extent, leucine to cells lacking Bat1 promotes cell division. Valine addition also increases TORC1 activity. In wild-type cells, TORC1 activity is dynamic in the cell cycle, starting low in early G1 but increasing later in the cell cycle. These results suggest a link between BCAA synthesis from glucose to TORC1 activation in the G1 phase of the cell cycle.
Schizophrenia (SCZ) can be described as a functional dysconnectivity syndrome that affects brain connectivity and circuitry. However, little is known about how sensory stimulation modulates network ...parameters in schizophrenia, such as their small-worldness (SW) during visual processing. To address this question, we applied graph theory algorithms to multi-electrode EEG recordings obtained during visual stimulation with a checkerboard pattern-reversal stimulus. Twenty-six volunteers participated in the study, 13 diagnosed with schizophrenia (SCZ; mean age = 38.3 years; SD = 9.61 years) and 13 healthy controls (HC; mean age = 28.92 years; SD = 12.92 years). The visually evoked potential (VEP) showed a global amplitude decrease (
p
< 0.05) for SCZ patients as opposed to HC but no differences in latency (
p
> 0.05). As a signature of functional connectivity, graph measures were obtained from the Magnitude-Squared Coherence between signals from pairs of occipital electrodes, separately for the alpha (8–13 Hz) and low-gamma (36–55 Hz) bands. For the alpha band, there was a significant effect of the visual stimulus on all measures (
p
< 0.05) but no group interaction between SCZ and HZ (
p
> 0.05). For the low-gamma spectrum, both groups showed a decrease of Characteristic Path Length (L) during visual stimulation (
p
< 0.05), but, contrary to the HC group, only SCZ significantly lowered their small-world (SW) connectivity index during visual stimulation (SCZ
p
< 0.05; HC
p
> 0.05). This indicates dysconnectivity of the functional network in the low-gamma band of SCZ during stimulation, which might indirectly reflect an altered ability to react to new sensory input in patients. These results provide novel evidence about a possible electrophysiological signature of the global deficits revealed by the application of graph theory onto electroencephalography in schizophrenia.
Fast gamma oscillations, generated within the retina, and transmitted to the cortex via the lateral geniculate nucleus (LGN), are thought to carry information about stimulus size and continuity. This ...hypothesis relies mainly on studies conducted under anesthesia and the extent to which it holds under more naturalistic conditions remains unclear. Using multielectrode recordings of spiking activity in the retina and the LGN of both male and female cats, we show that visually driven gamma oscillations are absent for awake states and are highly dependent on halothane (or isoflurane). Under ketamine, responses were nonoscillatory, as in the awake condition. Response entrainment to the monitor refresh was commonly observed up to 120 Hz and was superseded by the gamma oscillatory responses induced by halothane. Given that retinal gamma oscillations are contingent on halothane anesthesia and absent in the awake cat, such oscillations should be considered artifactual, thus playing no functional role in vision.
Gamma rhythms have been proposed to be a robust encoding mechanism critical for visual processing. In the retinogeniculate system of the cat, many studies have shown gamma oscillations associated with responses to static stimuli. Here, we extend these observations to dynamic stimuli. An unexpected finding was that retinal gamma responses strongly depend on halothane concentration levels and are absent in the awake cat. These results weaken the notion that gamma in the retina is relevant for vision. Notably, retinal gamma shares many of the properties of cortical gamma. In this respect, oscillations induced by halothane in the retina may serve as a valuable preparation, although artificial, for studying oscillatory dynamics.
Strains of
cause detrimental diarrheas with thousands of deaths worldwide. The infection process by the Gram-positive, strictly anaerobic gut bacterium is directly related to its unique metabolism, ...using multiple Stickland-type amino acid fermentation reactions coupled to Rnf complex-mediated sodium/proton gradient formation for ATP generation. Major pathways utilize phenylalanine, leucine, glycine and proline with the formation of 3-phenylproprionate, isocaproate, butyrate, 5-methylcaproate, valerate and 5-aminovalerate. In parallel a versatile sugar catabolism including pyruvate formate-lyase as a central enzyme and an incomplete tricarboxylic acid cycle to prevent unnecessary NADH formation completes the picture. However, a complex gene regulatory network that carefully mediates the continuous adaptation of this metabolism to changing environmental conditions is only partially elucidated. It involves the pleiotropic regulators CodY and SigH, the known carbon metabolism regulator CcpA, the proline regulator PrdR, the iron regulator Fur, the small regulatory RNA CsrA and potentially the NADH-responsive regulator Rex. Here, we describe the current knowledge of the metabolic principles of energy generation by
and the underlying gene regulatory scenarios.
The measurement of circulating nucleic acids has transformed the management of chronic viral infections such as HIV. The development of analogous markers for individuals with cancer could similarly ...enhance the management of their disease. DNA containing somatic mutations is highly tumor specific and thus, in theory, can provide optimum markers. However, the number of circulating mutant gene fragments is small compared to the number of normal circulating DNA fragments, making it difficult to detect and quantify them with the sensitivity required for meaningful clinical use. In this study, we applied a highly sensitive approach to quantify circulating tumor DNA (ctDNA) in 162 plasma samples from 18 subjects undergoing multimodality therapy for colorectal cancer. We found that ctDNA measurements could be used to reliably monitor tumor dynamics in subjects with cancer who were undergoing surgery or chemotherapy. We suggest that this personalized genetic approach could be generally applied to individuals with other types of cancer.
Histone 3 lysine 4 (H3K4) methylation is a universal epigenetic mark. In mammals, there are six H3K4 methyltransferases related to yeast Set1 and fly Trithorax, including two orthologs of Set1: ...Setd1a and Setd1b. Here we show that mouse Setd1a is required for gastrulation, whereas Setd1b-deficient embryos survive to E11.5 but are grossly retarded. Setd1a knockout embryos implant but do not proceed past the epiblast. Furthermore, Setd1a is not required until the inner cell mass has formed, at which stage it has replaced Mll2 as the major H3K4 methyltransferase. Setd1a is required for embryonic, epiblast and neural stem cell survival and neural stem cell reprogramming, whereas Setd1b is dispensable. Deletion of Setd1a in embryonic stem cells resulted in rapid losses of bulk H3K4 methylation, pluripotency gene expression and proliferation, with G1 pileup. Setd1b overexpression could not rescue the proliferation defects caused by loss of Setd1a in embryonic stem cells. The precise developmental requirement for Setd1a suggests that gastrulation is regulated by a switch between the major H3K4 methyltransferases.
Arthropods in amber from the Triassic Period Schmidt, Alexander R; Jancke, Saskia; Lindquist, Evert E ...
Proceedings of the National Academy of Sciences,
09/2012, Volume:
109, Issue:
37
Journal Article
Peer reviewed
Open access
The occurrence of arthropods in amber exclusively from the Cretaceous and Cenozoic is widely regarded to be a result of the production and preservation of large amounts of tree resin beginning ca. ...130 million years (Ma) ago. Abundant 230 million-year-old amber from the Late Triassic (Carnian) of northeastern Italy has previously yielded myriad microorganisms, but we report here that it also preserves arthropods some 100 Ma older than the earliest prior records in amber. The Triassic specimens are a nematoceran fly (Diptera) and two disparate species of mites, Triasacarus fedelei gen. et sp. nov., and Ampezzoa triassica gen. et sp. nov. These mites are the oldest definitive fossils of a group, the Eriophyoidea, which includes the gall mites and comprises at least 3,500 Recent species, 97% of which feed on angiosperms and represents one of the most specialized lineages of phytophagous arthropods. Antiquity of the gall mites in much their extant form was unexpected, particularly with the Triassic species already having many of their present-day features (such as only two pairs of legs); further, it establishes conifer feeding as an ancestral trait. Feeding by the fossil mites may have contributed to the formation of the amber droplets, but we find that the abundance of amber during the Carnian (ca. 230 Ma) is globally anomalous for the pre-Cretaceous and may, alternatively, be related to paleoclimate. Further recovery of arthropods in Carnian-aged amber is promising and will have profound implications for understanding the evolution of terrestrial members of the most diverse phylum of organisms.
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