A genetic marker in the variable region of rabbit immunoglobulin heavy chain.

A previous study [Mole et al. (1971) Biochem. J. 124, 301-318] showed several differences in sequence between the variable (V) regions of rabbit immunoglobulin Aa1 and Aa3 heavy chains. The inheritance of one such difference has been followed in a family of 38 rabbits by a radioautographic peptide-'map' technique and is shown to segregate in a Mendelian fashion. This clearly demonstrates the presence of a genetic marker in the rabbit heavy-chain V region, although the finding that Aa2 and Aa3 heavy chains have identity of sequence in the region studied obscures the relationship of this genetic marker to the a locus.     

Cholinergic interneurons in the feeding system of the pond snail Lymnaea stagnalis. II. N1 interneurons make cholinergic synapses with feeding motoneurons.

The N1 neurons are a population of interneurons active during the protraction phase of the feeding rhythm. All the N1 neurons are coupled by electrical synapses which persist in a high Mg/low Ca saline which blocks chemical synapses. Individual N1 spikes produce discrete electrotonic postsynaptic potentials (PSPS) in other N1 cells, but the coupling is not strong enough to ensure 1:1 firing. Bursts of N1 spikes generate compound PSPS in the feeding motoneurons. The sign (excitation or inhibition) of the N1 input corresponds with the synaptic barrage recorded during the protraction phase. Discrete PSPS are only resolved in a Hi-Di saline. Their variation in latency and number can be explained by variation in electrotonic propagation within the electrically coupled network of N1 cells. The excitatory postsynaptic potentials (ESPS) in the 1 cell are reduced by 0.5 mM antagonists hexamethonium (HMT), atropine (ATR), curare (d-TC) and by methylxylocholine (MeXCh), all of which block the excitatory cholinergic receptor (Elliott et al. (Phil. Trans. R. Soc. Lond. 336, 157-166 (Preceding paper.) (1992)). The 1 cell EPSPS were transiently blocked by phenyltrimethylammonium (PTMA), which is both an agonist and antagonist at the 1 cell excitatory acetylcholine (ACh) receptor (Elliott et al. 1992). The inhibitory postsynaptic potential (IPSP) in the 3 cell is blocked by bath applications of MeXCh and PTMA, which both abolish the response of the 3 cell to ACh (Elliott et. al. 1992). The effects of the cholinergic antagonists on the response of 4 cluster and 5 cells to N1 stimulation matches their response to ACh (Elliott et al. 1992). It is concluded that the population of N1 cells are multiaction, premotor cholinergic interneurons.     

The bimodal auditory-vibratory system of the thoracic ventral nerve cord in Locusta migratoria (Acrididae, Locustinae, Oedipodini).

In locusts the auditory receptors of the tympanal organs and many of the vibratory receptors of all 6 legs converge at the level of the thoracic ventral nerve cord, forming a combined auditory-vibratory sensory system; it is represented by the VS-, S-, and V-neurons ascending to the supraesophageal ganglion. The connections between vibratory receptors of the different legs and the dendritic inputs of the bimodal ascending neurons are investigated in this report. As an example, the dendritic branches of the G- and V3-neurons for auditory and vibratory input could be localized by simultaneous recording at 2 different positions of the axon. The vibratory input from the receptors of the different legs was determined. Segmental and/or intersegmental thoracic interneurons are intercalated between the receptors and the ascending auditory-vibratory neurons (G- and V3-neurons). The morphology and function of 2 intersegmental vibratory interneurons (VI1- and VI2-neurons) are described. They probably connect the vibratory receptors of 1 (or 2) leg(s) of 1 thoracic segment with the different bimodal auditory-vibratory neurons. The importance of the anterior Ring Tract for synaptic connection between receptor cells, first order interneurons, and bimodal auditory-vibratory neurons is discussed on the basis of morphological and physiological data.     

192 Computer-aided search for novel anti-HIV-1 agents presenting peptidomimetics of broadly neutralizing antibodies against the virus envelope GP120 V3 loop

Computer-aided search for novel anti-HIV-1 agents that are able to imitate the pharmacophore properties of the antigen-binding site of a broadly neutralizing mAb 3074 against the envelope gp120 V3 loop was carried out followed by evaluation of their potential inhibitory activity by molecular modeling. In doing so, the following problems were solved: (1) the mAb 3074 amino acid residues responsible for specific binding to the HIV-1 V3 loop were identified from the X-ray structures of this antibody Fab in complexes with the MN, UR29, and VI191 V3 peptides (Jiang et al., 2010); (2) using these data, 2039 possible mAb-3074 peptidomimetics were found by pepMMsMIMIC presenting a public, web-oriented virtual screening platform (Floris et al., 2011); (3) the complexes of these compounds with the above V3 peptides were built by molecular docking and, based on their analysis, the four molecules exhibiting a high affinity to V3 in the in silico studies were selected as the most probable peptidomimetics of mAb 3074 (Figure 1); and (4) stability of the complexes of these molecules with the MN, UR29, and VI191 V3 peptides was estimated by molecular dynamics and free energy simulations. As a result, a key role in specific binding of the selected compounds to the V3 loop was shown to belong to π-π interactions between their aromatic rings and the conserved Phe20 and/or Tyr21 of the V3 immunogenic crown. Similarly to mAb 3074, these compounds were found to block the tip of the V3 loop forming its invariant structural motif, which contains residues critical for cell tropism (Andrianov et al., 2011; Andrianov et al., 2012). In addition, the complexes of interest do not undergo significant changes within the molecular dynamics calculations, exhibiting the low values of free energy of their formation. In this context, the compounds given in Figure 1 are considered as the promising basic structures for the design of novel, potent, and broad anti-HIV-1 drugs.     

Keeping inhibition timely

GABAergic interneurons play a key role in orchestrating cortical network oscillations. In this issue of Neuron, two studies (Bacci and Huguenard and Vida et al.) identify how networks of fast-spiking interneurons can enhance the regularity, precision, and robustness of their own rhythmicity via individual and collective self-innervation.     

Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity.

The homeobox gene Hb9, like its close relative MNR2, is expressed selectively by motor neurons (MNs) in the developing vertebrate CNS. In embryonic chick spinal cord, the ectopic expression of MNR2 or Hb9 is sufficient to trigger MN differentiation and to repress the differentiation of an adjacent population of V2 interneurons. Here, we provide genetic evidence that Hb9 has an essential role in MN differentiation. In mice lacking Hb9 function, MNs are generated on schedule and in normal numbers but transiently acquire molecular features of V2 interneurons. The aberrant specification of MN identity is associated with defects in the migration of MNs, the emergence of the subtype identities of MNs, and the projection of motor axons. These findings show that HB9 has an essential function in consolidating the identity of postmitotic MNs.     

Exciting information for inhibitory neurons

One unsolved issue in brain development is how interneurons migrating tangentially into the cortex acquire their regional addresses and laminar positions. The study by Lodato et al. in this issue shows that projection neurons regulate the laminar fates of cortical interneurons.     

MHC-dependent mate choice in humans: why genomic patterns from the HapMap European American dataset support the hypothesis

The role of the major histocompatibility complex (MHC) in mate choice in humans is controversial. Nowadays, the availability of genetic variation data at genomic scales allows for a careful assessment of this question. In 2008, Chaix et al. reported evidence for MHC-dependent mate choice among European American spouses from the HapMap 2 dataset. Recently, Derti et al. suggested that this observation was not robust. Furthermore, when Derti et al. applied similar analyses to the HapMap 3 European American samples, they did not see a significant effect. Although some of the points raised by Derti et al. are relevant, we disagree with the reported absence of evidence for MHC-dependent mate choice within the HapMap samples. More precisely, we show here that the MHC dissimilarity among HapMap 3 European American spouses is still extreme in comparison to the rest of the genome, even after multiple testing correction. This finding supports the hypothesis of MHC-dependent mate choice in some human populations.     

Elongation factor 2 and fragile X mental retardation protein control the dynamic translation of Arc/Arg3.1 essential for mGluR-LTD

The initiation and coordination of activity in limb muscles are the main functions of neural circuits that control locomotion. Commissural neurons connect locomotor circuits on the two sides of the spinal cord, and represent the known neural substrate for left-right coordination. Here we demonstrate that a group of ipsilateral interneurons, V2a interneurons, plays an essential role in the control of left-right alternation. In the absence of V2a interneurons, the spinal cord fails to exhibit consistent left-right alternation. Locomotor burst activity shows increased variability, but flexor-extensor coordination is unaffected. Anatomical tracing studies reveal a direct excitatory input of V2a interneurons onto commissural interneurons, including a set of molecularly defined V0 neurons that drive left-right alternation. Our findings imply that the neural substrate for left-right coordination consists of at least two components; commissural neurons and a class of ipsilateral interneurons that activate commissural pathways.     

Otx2's incredible journey

A surprising new mechanism that regulates the plasticity of postnatal neurons is reported in this issue by Sugiyama et al. (2008). These authors show in mice that visual experience triggers cell-to-cell transfer of the homeoprotein Otx2 to cortical interneurons, where it promotes maturation of inhibitory neural circuitry and opens the critical period for plasticity in the visual cortex.     

Convergent evolution of SARS-CoV-2 in human and animals

Recently,many SARS-CoV-2 variants including 501Y.V1,501Y.V2 and 501Y.V3 were detected in different regions(Table S1)and drew great attention from all over the world.The 501Y.V1 was firstly isolated in the United Kingdom(UK)(Davies et al.,2020)and featured with 7 substitutions including N501Y as well as 3 deletions in S protein.This variant was identified to increase the viral transmissibility by 56％in comparison with the preexisting strains.Days after this report,another SARS-CoV-2 variant(501Y.V2)featured with N501Y,K417N and E484K substitutions in S protein was supposed to rapidly outcompete the preexisting strains(Tegally et al.,2020)in South Africa.Besides,the 501Y.V3 variant was initially detected in Brazil and has caused rapidly increased infections with SNPs N501Y,K417T and E484K.Of them,N501Y,K417N/T and E484K are of particular interest because the N501Y was shared in all three variants and the K417N/T and E484K were detected simultaneous appeared with N501Y in 501Y.V2 and 501Y.V3.     

Histochemistry and functional significance of putative neocortical transmitter substances: a review

1. Intrinsic neuronal chains of the neocortex communicate most probably with amino acid transmitters. These involve both excitatory (glutamate, aspartate--Nadler et al. 1976) both inhibitory (GABA--Ribak 1978) amino acids, and ensure fast, ionotropic postsynaptic actions (Eccles, McGeer 1979). 2. Some interneurons of the neocortex seemingly operate with the peptide transmitter VIP (Lorén et al. 1979). Presumably, this is a metabotropic, slowly acting substance (Dodd, Kelly and Said 1979). 3. The existence of intrinsic cholinergic neurons in the neocortex is a matter of question (Krnjevic and Silver 1965). It is worth to mention that in the periphery, cholinergic terminals also contain and release VIP (H?kfelt et al. 1980). It is not known, whether this transmitter dualism can be found in neocortex, too. An ascending cholinergic system projecting from the basal forebrain to the neocortex exists and exerts profound influence on cortical function (Shute and Lewis 1967). 4. Diffusely terminating, ascending monoamine axons innervate the neocortex and modulate interneuronal transmission (Thiery et al. 1977; Morrison et al. 1981, Lidov et al. 1981). 5. The neuropeptide SP excites cortical neurons (Phillis and Limacher 1974), and its presence in thin axons can be demonstrated immunohistochemically (H?kfelt et al. 1976). 6. Neocortical efferents to the thalamus and striatum seemingly use glutamate or aspartate (Fonnum et al. 1981). The transmitters of other corticofugal projections are not known. 7. The transmitters of specific thalamic afferents and those of callosal and association projections are unknown, too. 8. The main task of future histochemistry is to explore the synaptology of neocortical neurons and afferent systems with identified or evidenced transmitters, viz. to explore the neurochemical subsystems of cortical organization. The tool for it could be the immunohistochemistry, and future development depends mainly on the synthesis and purification of suitable antigens. The knowledge on the synaptology of identified neurochemical units of the cortex would be the basis of the understanding at least partly of the pharmacological effects exerted by the putative neocortical transmitters.     

The Greek Goddess,Artemis, reveals the secrets of her cleavage

A recent paper in Cell by Ma et al. [Cell 8 (2002) 781] showed that the protein Artemis cleaves a hairpin intermediate during V(D)J recombination. Peter O'Neill and Penny Jeggo discuss this finding in the light of evidence that Artemis also functions to repair radiation damage [Cell 105 (2001) 177]. The findings suggest that Artemis may function in double strand break repair by "tidying up" double strand ends with associated base damage. The development of genetic diversity during immune development, therefore, seems to exploit damage response mechanisms that function to maintain genetic stability in other cell lineages.     

关于董氏狼鳍鱼(Lycoptera tungi)的种上归类

本文重新研究了董氏狼鳍鱼 (Lycoptera tungi Liu et al 1963).将产自宁夏隆德石窑寺的董氏狼鳍鱼 V2323 号标本从狼鳍鱼属 (Lycoptera) 中分出来,归入华夏鱼属 (Huashia), 修定为董氏华夏鱼 (Huashia tungi (Liu et al.)).同时对华夏鱼科 (Huashiidae) 的系统位置作了初步讨论.