Catálogo de publicaciones - revistas

<jats:p>The hippocampal CA3 region plays a key role in learning and memory. Recurrent CA3–CA3 synapses are thought to be the subcellular substrate of pattern completion. However, the synaptic mechanisms of this network computation remain enigmatic. To investigate these mechanisms, we combined functional connectivity analysis with network modeling. Simultaneous recording from up to eight CA3 pyramidal neurons revealed that connectivity was sparse, spatially uniform, and highly enriched in disynaptic motifs (reciprocal, convergence, divergence, and chain motifs). Unitary connections were composed of one or two synaptic contacts, suggesting efficient use of postsynaptic space. Real-size modeling indicated that CA3 networks with sparse connectivity, disynaptic motifs, and single-contact connections robustly generated pattern completion. Thus, macro- and microconnectivity contribute to efficient memory storage and retrieval in hippocampal networks.</jats:p>

<jats:p>Inhibitory synapses dampen neuronal activity through postsynaptic hyperpolarization. The composition of the inhibitory postsynapse and the mechanistic basis of its regulation, however, remain poorly understood. We used an in vivo chemico-genetic proximity-labeling approach to discover inhibitory postsynaptic proteins. Quantitative mass spectrometry not only recapitulated known inhibitory postsynaptic proteins but also revealed a large network of new proteins, many of which are either implicated in neurodevelopmental disorders or are of unknown function. Clustered regularly interspaced short palindromic repeats (CRISPR) depletion of one of these previously uncharacterized proteins, InSyn1, led to decreased postsynaptic inhibitory sites, reduced the frequency of miniature inhibitory currents, and increased excitability in the hippocampus. Our findings uncover a rich and functionally diverse assemblage of previously unknown proteins that regulate postsynaptic inhibition and might contribute to developmental brain disorders.</jats:p>

<jats:p>Zika virus (ZIKV) is responsible for a major ongoing epidemic in the Americas and has been causally associated with fetal microcephaly. The development of a safe and effective ZIKV vaccine is therefore an urgent global health priority. Here we demonstrate that three different vaccine platforms protect against ZIKV challenge in rhesus monkeys. A purified inactivated virus vaccine induced ZIKV-specific neutralizing antibodies and completely protected monkeys against ZIKV strains from both Brazil and Puerto Rico. Purified immunoglobulin from vaccinated monkeys also conferred passive protection in adoptive transfer studies. A plasmid DNA vaccine and a single-shot recombinant rhesus adenovirus serotype 52 vector vaccine, both expressing ZIKV premembrane and envelope, also elicited neutralizing antibodies and completely protected monkeys against ZIKV challenge. These data support the rapid clinical development of ZIKV vaccines for humans.</jats:p>

<jats:p>Aftershocks are often triggered by static- and/or dynamic-stress changes caused by mainshocks. The relative importance of the two triggering mechanisms is controversial at near-to-intermediate distances. We detected and located 48 previously unidentified large early aftershocks triggered by earthquakes with magnitudes between ≥7 and 8 within a few fault lengths (approximately 300 kilometers), during times that high-amplitude surface waves arrive from the mainshock (less than 200 seconds). The observations indicate that near-to-intermediate-field dynamic triggering commonly exists and fundamentally promotes aftershock occurrence. The mainshocks and their nearby early aftershocks are located at major subduction zones and continental boundaries, and mainshocks with all types of faulting-mechanisms (normal, reverse, and strike-slip) can trigger early aftershocks.</jats:p>

<jats:p> Materials with good flexibility and high conductivity that can provide electromagnetic interference (EMI) shielding with minimal thickness are highly desirable, especially if they can be easily processed into films. Two-dimensional metal carbides and nitrides, known as MXenes, combine metallic conductivity and hydrophilic surfaces. Here, we demonstrate the potential of several MXenes and their polymer composites for EMI shielding. A 45-micrometer-thick Ti <jats:sub>3</jats:sub> C <jats:sub>2</jats:sub> T <jats:sub>x</jats:sub> film exhibited EMI shielding effectiveness of 92 decibels (&gt;50 decibels for a 2.5-micrometer film), which is the highest among synthetic materials of comparable thickness produced to date. This performance originates from the excellent electrical conductivity of Ti <jats:sub>3</jats:sub> C <jats:sub>2</jats:sub> T <jats:sub>x</jats:sub> films (4600 Siemens per centimeter) and multiple internal reflections from Ti <jats:sub>3</jats:sub> C <jats:sub>2</jats:sub> T <jats:sub>x</jats:sub> flakes in free-standing films. The mechanical flexibility and easy coating capability offered by MXenes and their composites enable them to shield surfaces of any shape while providing high EMI shielding efficiency. </jats:p>

<jats:p>Highly siderophile elements (HSEs) are strongly depleted in the bulk silicate Earth (BSE) but are present in near-chondritic relative abundances. The conventional explanation is that the HSEs were stripped from the mantle by the segregation of metal during core formation but were added back in near-chondritic proportions by late accretion, after core formation had ceased. Here we show that metal-silicate equilibration and segregation during Earth’s core formation actually increased HSE mantle concentrations because HSE partition coefficients are relatively low at the high pressures of core formation within Earth. The pervasive exsolution and segregation of iron sulfide liquid from silicate liquid (the “Hadean matte”) stripped magma oceans of HSEs during cooling and crystallization, before late accretion, and resulted in slightly suprachondritic palladium/iridium and ruthenium/iridium ratios.</jats:p>

<jats:p> Primary and <jats:italic>N</jats:italic> -alkyl arylamine motifs are key functional groups in pharmaceuticals, agrochemicals, and functional materials, as well as in bioactive natural products. However, there is a dearth of generally applicable methods for the direct replacement of aryl hydrogens with NH <jats:sub>2</jats:sub> /NH(alkyl) moieties. Here, we present a mild dirhodium-catalyzed C-H amination for conversion of structurally diverse monocyclic and fused aromatics to the corresponding primary and <jats:italic>N</jats:italic> -alkyl arylamines using NH <jats:sub>2</jats:sub> /NH(alkyl)- <jats:italic>O</jats:italic> -(sulfonyl)hydroxylamines as aminating agents; the relatively weak RSO <jats:sub>2</jats:sub> O-N bond functions as an internal oxidant. The methodology is operationally simple, scalable, and fast at or below ambient temperature, furnishing arylamines in moderate-to-good yields and with good regioselectivity. It can be readily extended to the synthesis of fused <jats:italic>N</jats:italic> -heterocycles. </jats:p>

<jats:p>A key aspect of bacterial survival is the ability to evolve while migrating across spatially varying environmental challenges. Laboratory experiments, however, often study evolution in well-mixed systems. Here, we introduce an experimental device, the microbial evolution and growth arena (MEGA)–plate, in which bacteria spread and evolved on a large antibiotic landscape (120 × 60 centimeters) that allowed visual observation of mutation and selection in a migrating bacterial front. While resistance increased consistently, multiple coexisting lineages diversified both phenotypically and genotypically. Analyzing mutants at and behind the propagating front, we found that evolution is not always led by the most resistant mutants; highly resistant mutants may be trapped behind more sensitive lineages. The MEGA-plate provides a versatile platform for studying microbial adaption and directly visualizing evolutionary dynamics.</jats:p>

<jats:p>The global expansion of the Internet is frequently associated with increased government transparency, political rights, and democracy. However, this assumption depends on marginalized groups getting access in the first place. Here we document a strong and persistent political bias in the allocation of Internet coverage across ethnic groups worldwide. Using estimates of Internet penetration obtained through network measurements, we show that politically excluded groups suffer from significantly lower Internet penetration rates compared with those in power, an effect that cannot be explained by economic or geographic factors. Our findings underline one of the central impediments to “liberation technology,” which is that governments still play a key role in the allocation of the Internet and can, intentionally or not, sabotage its liberating effects.</jats:p>