Relationships among msx gene structure and function in zebrafish and other vertebrates

The zebrafish genome contains at least five msx homeobox genes, msxA, msxB, msxC, msxD, and the newly isolated msxE. Although these genes share structural features common to all Msx genes, phylogenetic analyses of protein sequences indicate that the msx genes from zebrafish are not orthologous to the Msx1 and Msx2 genes of mammals, birds, and amphibians. The zebrafish msxB and msxC are more closely related to each other and to the mouse Msx3. Similarly, although the combinatorial expression of the zebrafish msx genes in the embryonic dorsal neuroectoderm, visceral arches, fins, and sensory organs suggests functional similarities with the Msx genes of other vertebrates, differences in the expression patterns preclude precise assignment of orthological relationships. Distinct duplication events may have given rise to the msx genes of modern fish and other vertebrate lineages whereas many aspects of msx gene functions during embryonic development have been preserved.      

The MMS22L–TONSL heterodimer directly promotes RAD51‐dependent recombination upon replication stress

Homologous recombination (HR) is a key pathway that repairs DNA double‐strand breaks (DSBs) and helps to restart stalled or collapsed replication forks. How HR supports replication upon genotoxic stress is not understood. Using in vivo and in vitro approaches, we show that the MMS22L–TONSL heterodimer localizes to replication forks under unperturbed conditions and its recruitment is increased during replication stress in human cells. MMS22L–TONSL associates with replication protein A (RPA)‐coated ssDNA, and the MMS22L subunit directly interacts with the strand exchange protein RAD51. MMS22L is required for proper RAD51 assembly at DNA damage sites in vivo, and HR‐mediated repair of stalled forks is abrogated in cells expressing a MMS22L mutant deficient in RAD51 interaction. Similar to the recombination mediator BRCA2, recombinant MMS22L–TONSL limits the assembly of RAD51 on dsDNA, which stimulates RAD51‐ssDNA nucleoprotein filament formation and RAD51‐dependent strand exchange activity in vitro. Thus, by specifically regulating RAD51 activity at uncoupled replication forks, MMS22L–TONSL stabilizes perturbed replication forks by promoting replication fork reversal and stimulating their HR‐mediated restart in vivo.     

Factors Related to Social Support in Neurological and Mental Disorders

Despite the huge body of research on social support, literature has been primarily focused on its beneficial role for both physical and mental health. It is still unclear why people with mental and neurological disorders experience low levels of social support. The main objective of this study was to explore what are the strongest factors related to social support and how do they interact with each other in neuropsychiatric disorders. The study used cross-sectional data from 722 persons suffering from dementia, depression, epilepsy, migraine, multiple sclerosis, Parkinson''s disease, schizophrenia, stroke, and substance use disorders. Multiple linear regressions showed that disability was the strongest factor for social support. Extraversion and agreeableness were significant personality variables, but when the interaction terms between personality traits and disability were included, disability remained the only significant variable. Moreover, level of disability mediated the relationship between personality (extraversion and agreeableness) and level of social support. Moderation analysis revealed that people that had mental disorders experienced lower levels of support when being highly disabled compared to people with neurological disorders. Unlike previous literature, focused on increasing social support as the origin of improving disability, this study suggested that interventions improving day-to-day functioning or maladaptive personality styles might also have an effect on the way people perceive social support. Future longitudinal research, however, is warranted to explore causality.     

The wake-sleep cycle in the cat following dorso-pontine lesions

Modifications in total amount, frequency and duration of episodes of wakefulness (W), drowsiness (D), slow sleep (SS) and paradoxal sleep (PS) were examined in cats with small unilateral lesion in the locus coeruleus (LC) and/or neighbouring structures. Throughout a 8 week period, 24 h weekly records were obtained from each cat. Control group with lesions in the dorsomedial pontine area showed a noticeable stability in sleep-wakefulness cycle (SWC). Significant decrease of W (with shortening of episodes) occurred during the whole postlesion period in the group with lesions in the lateral vestibular nucleus. The group with small lesions restricted to the dorsal-intermediate part of RPO and RPC nuclei had only acute SWC modifications consisting of a decrease of W and increase of PS. Finally, small lesions in LC complex that encroached to a limited extent neighbouring structures produced a maintained decrease of W (with shortening of episodes) and increase of PS (due to a major number of episodes). Results suggest a different role of dorsopontine region from other pontine areas in SWC mechanisms and give support to the hypothesis of a permissive role of LC in PS mechanisms.     

Effects of EDTA treatment upon the protein subunit composition and mechanical properties of mammalian single skeletal muscle fibers

Considerable interest has been focused on the role of myosin light chain LC(2) in the contraction of vertebrate striated muscle. A study was undertaken to further our investigations (Moss, R.L., G.G. Giulian, and M.L. Greaser, 1981, J. Biol. Chem., 257:8588-8591) of the effects of LC(2) removal upon contraction in skinned fibers from rabbit psoas muscles. Isometric tension and maximum velocity of shortening, V(max), were measured in fiber segments prior to LC(2) removal. The segments were then bathed at 30 degrees C for up to 240 min in a buffer solution containing 20 mM EDTA in order to extract up to 60 percent of the LC(2). Troponin C (TnC) was also partially removed by this procedure. Mechanical measurements were done following the EDTA extraction and the readditions of first TnC and then LC(2) to the segments. The protein subunit compositions of the same fiber segments were determined following each of these procedures by SDS PAGE of small pieces of the fiber. V(max) was found to decrease as the LC(2) content of the fiber segments was reduced by increasing the duration of extraction. EDTA treatment also resulted in substantial reductions in tension due mainly to the loss of TnC, though smaller reductions due to the extraction of LC(2) were also observed. Reversal of the order of recombination of LC(2) and TnC indicated that the reduction in V(max) following EDTA treatment was a specific effect of LC(2) removal. These results strongly suggest that LC(2) may have roles in determining the kinetics and extent of interaction between myosin and actin.     

Nucleotide sequence analysis of the lemur beta-globin gene family: evidence for major rate fluctuations in globin polypeptide evolution

Lemur beta-related globin genes have been isolated and sequenced. Orthology of prosimian and human epsilon-, gamma-, and beta-related globin genes was established by dot-matrix analysis. All of these lemur globin genes potentially encode functional beta-related globin polypeptides, though precisely when the gamma-globin gene is expressed remains unknown. The organization of the 18-kb brown lemur beta-globin gene cluster (5' epsilon-gamma-[psi eta-delta]-beta 3') is consistent with its evolution by contraction via unequal crossing-over from the putative ancestral mammalian beta-globin gene cluster (5' epsilon-gamma- eta-delta-beta 3'). The dwarf lemur nonadult globin genes are arranged as in the brown lemur. Similar levels of synonymous (silent) nucleotide substitutions and noncoding DNA sequence differences have accumulated between species in all of these genes, suggesting a uniform rate of noncoding DNA divergence throughout primate beta-globin gene clusters. These differences are comparable with those observed in the nonfunctional psi eta pseudogene and have therefore accumulated at the presumably maximal neutral rate. In contrast, nonsynonymous (replacement) nucleotide substitutions show a significant heterogeneity in distribution for both the same gene in different lineages and different genes in the same lineage. These major fluctuations in replacement but not silent substitution rates cannot be attributed to changes in mutation rate, suggesting that changes in the rate of globin polypeptide evolution in primates is not governed solely by variable mutation rates.      

The physiological basis of seed dormancy in Avena fatua. II. On the involvement of alternative respiration in the stimulation of germination by sodium azide

Chromatography on DEAE-cellulose of an extract from etiolated leaves of sorghum ( Sorghum vulgare Pers. cv. INRA 450), a C₄ plant, gave only one form of phosphoenol pyruvate carboxylase with functional and regulatory properties of a C₃ type plant enzyme. Greening of the leaves resulted in a significant increase in activity. This increase was due to the appearance of a new form of the enzyme, which eluted at lower ionic strength and exhibited new properties. This form was glucose-6-P activated and showed a sigmoidal curve response to the concentration of the substrate phosphoerralpyruvate. These kinetic properties are typical of a C₄ plant enzyme.     

Effects of temperature,oxygen concentration,leaf age and seasonal variations on the CO2 compensation point of Lolium perenne L.

Various factors affect the CO₂ compensation point of detached leaves of Lolium perenne L. These include oxygen concentration, temperature, leaf age, and season (spring and summer). Analysis of the results using the model of G.D. Farquhar, S. von Caemmerer and J.A. Berry (1980) Planta 149, 78–90, indicates that some of the CO₂ evolved by leaves in the light is derived from sources other than photorespiration. It is suggested that the operation of the tricarboxylic acid in the light can account for most of this CO₂.Azcón-Bieto—experimental work was done in Barcelona, the further analyses white at the A.N.U.     

Bone marrow histopathologic patterns and immunologic phenotype in B-cell chronic lymphocytic leukaemia

The present work analyzes the clinicobiological and immunological characteristics - the latter hitherto unexplored - of the different bone marrow histopathological patterns of the B-cell chronic lymphocytic leukaemia (B-CLL). In addition, we studied whether any or some of these parameters were able to predict the probability of a particular pattern of bone marrow involvement appearing. Of the 100 B-CLL cases studied 41 had a diffuse pattern and 59 were non-diffuse - interstitial 27, nodular 11 and mixed 21 -. Neither clinical nor immunological differences were observed among the distinct non-diffuse patterns. The patients in the diffuse group displayed an increased incidence of mu+ isotype and a higher proportion of HLA-DR and HAN-PC 1 positive cells while, conversely, reactivity with the FMC 8 McAb was lower. In addition, patients with a diffuse pattern of BM involvement displayed features of a more extensive disease: a higher incidence of adenopathies (p less than 0.05), hepatomegaly (p less than 0.01), splenomegaly (p less than 0.01), anaemia (p less than 0.01) and thrombopenia (p less than 0.01) as well as higher levels of peripheral blood lymphocytosis (p less than 0.05) and a higher percentage of BM lymphocytic infiltration (p less than 0.001). Multiple regression analysis showed that thrombopenia and splenomegaly were the two most important features in predicting the probability of a diffuse pattern.