Evidence Of Functional Differences Research Articles

Chromatin activity identifies differential gene regulation across human ancestries

BackgroundCurrent evidence suggests that cis-regulatory elements controlling gene expression may be the predominant target of natural selection in humans and other species. Detecting selection acting on these elements is critical to understanding evolution but remains challenging because we do not know which mutations will affect gene regulation.ResultsTo address this, we devise an approach to search for lineage-specific selection on three critical steps in transcriptional regulation: chromatin activity, transcription factor binding, and chromosomal looping. Applying this approach to lymphoblastoid cells from 831 individuals of either European or African descent, we find strong signals of differential chromatin activity linked to gene expression differences between ancestries in numerous contexts, but no evidence of functional differences in chromosomal looping. Moreover, we show that enhancers rather than promoters display the strongest signs of selection associated with sites of differential transcription factor binding.ConclusionsOverall, our study indicates that some cis-regulatory adaptation may be more easily detected at the level of chromatin than DNA sequence. This work provides a vast resource of genomic interaction data from diverse human populations and establishes a novel selection test that will benefit future study of regulatory evolution in humans and other species.

Bioactivities of endophytic actinobacteria inhabiting Artemisia herba-alba emphasizing differences from free-living strains.

The endophytic actinobacteria associated with Artemisia herba-alba (synonym: Seriphidium herba-alba) are highly diverse. This study aimed to illustrate the extent of their differences from the free-living actinobacteria in the surrounding environment. A selection of eighteen actinobacteria inhabiting A. herba-alba were compared with twenty and ten actinobatceria isolates from the surrounding desert and groundwater, respectively, representing six genera. Antagonistic and enzymatic activities, plant growth-promoting traits, and the occurrence of biosynthetic genes were compared among the isolates. Data were analyzed statistically using principal component analysis (PCA) and were visualized using heat map. Endophytic strains showed higher antimicrobial activity and production of plant growth promoters compared to desert and groundwater strains. Polyketide synthase and non-ribosomal peptide synthetase gene clusters were detected at higher frequencies in the endophytic strains (8 and 11 strains, respectively) than the desert strains (1 and 2 strains, respectively). In contrast, both gene clusters were not detected in the groundwater strains. The PCA revealed unique metabolic characteristics of the endophytes. The heatmap clustered the endophytic strains apart from the free-living strains, indicating distinctive qualitative and quantitative bioactivities. Analysis of 16S rRNA genes confirmed the chemotaxonomic identity of all but two strains, with > 94.5% similarity. Six endophytes displayed < 99.5% similarity with their closest type strains, which might indicate species novelty. This study provides an evidence of functional differences and possible species novelty of the endophytic actinobacteria inhabiting A. herba-alba, compared with the free-living species.

Surveillance for SARS-CoV-2 variants of concern in the Australian context.

Surveillance for SARS-CoV-2 variants of concern in the Australian context.

Asymmetric cross-hemispheric connections link the rat anterior thalamic nuclei with the cortex and hippocampal formation

Dense reciprocal connections link the rat anterior thalamic nuclei with the prelimbic, anterior cingulate and retrosplenial cortices, as well as with the subiculum and postsubiculum. The present study compared the ipsilateral thalamic-cortical connections with the corresponding crossed, contralateral connections between these same sets of regions. All efferents from the anteromedial thalamic nucleus to the cortex, as well as those to the subiculum, remained ipsilateral. In contrast, all of these target sites provided reciprocal, bilateral projections to the anteromedial nucleus. While the anteroventral thalamic nucleus often shared this same asymmetric pattern of cortical connections, it received relatively fewer crossed inputs than the anteromedial nucleus. This difference was most marked for the anterior cingulate projections, as those to the anteroventral nucleus remained almost entirely ipsilateral. Unlike the anteromedial nucleus, the anteroventral nucleus also appeared to provide a restricted, crossed projection to the contralateral retrosplenial cortex. Meanwhile, the closely related laterodorsal thalamic nucleus had almost exclusively ipsilateral efferent and afferent cortical connections. Likewise, within the hippocampus, the postsubiculum seemingly had only ipsilateral efferent and afferent connections with the anterior thalamic and laterodorsal nuclei. While the bilateral cortical projections to the anterior thalamic nuclei originated predominantly from layer VI, the accompanying sparse projections from layer V largely gave rise to ipsilateral thalamic inputs. In testing a potentially unifying principle of anterior thalamic – cortical interactions, a slightly more individual pattern emerged that reinforces other evidence of functional differences within the anterior thalamic and also helps to explain the consequences of unilateral interventions involving these nuclei.

Effect of handedness on fMRI activation in the medial temporal lobe during an auditory verbal memory task

Several studies have shown marked differences in the neural localization of language functions in the brains of left-handed individuals when compared with right-handers. Previous experiments involving functional lateralization have demonstrated cerebral blood flow patterns that differ concordantly with subject handedness while performing language-related tasks. The effect of handedness on function in specific stages of memory processing, however, is a largely unexplored area. We used a paired-associates verbal memory task to elicit activation of neural areas related to declarative memory, examining the hypothesis that there are differences in activation in the medial temporal lobe (MTL) between handedness groups. 15 left-handed and 25 right-handed healthy adults were matched for all major demographic and neuropsychological variables. Functional and structural imaging data were acquired and analyzed for group differences within MTL subregions. Our results show that activation of the MTL during declarative memory processing varies with handedness. While both groups showed activation in left and right MTL subregions, the left-handed group showed a statistically significant increase in the left hippocampus and amygdala during both encoding and recall. No increases in activation were found in the right-handed group. This effect was found in the absence of any differences in performance on the verbal memory task, structural volumetric disparities, or functional asymmetries. This provides evidence of functional differences between left-handers and right-handers, which extends to declarative memory processes.

Temporal and spatial infection dynamics indicate recognition events in the early hours of a dinoflagellate/coral symbiosis

The obligate symbiotic relationship between dinoflagellates, Symbiodinium spp. and reef building corals is re-established each host generation. The solitary coral Fungia scutaria Lamarck 1801 harbors a single algal strain, Symbiodinium ITS2 type C1f (homologous strain) during adulthood. Previous studies have shown that distinct algal ITS2 types in clade C correlate with F. scutaria—Symbiodinium specificity during the onset of symbiosis in the larval stage. The present study examined the early specificity events in the onset of symbiosis between F. scutaria larvae and Symbiodinium spp., by looking at the temporal and spatial infection dynamics of larvae challenged with different symbiont types. The results show that specificity at the onset of symbiosis was mediated by recognition events during the initial symbiont—host physical contact before phagocytosis, and by subsequent cellular events after the symbionts were incorporated into host cells. Moreover, homologous and heterologous Symbiodinium sp. strains did not exhibit the same pattern of localization within larvae. When larvae were infected with homologous symbionts (C1f), ~70% of the total acquired algae were found in the equatorial area of the larvae, between the oral and aboral ends, 21 h after inoculation. In contrast, no spatial difference in algal localization was observed in larvae infected with heterologous symbionts. This result provides evidence of functional differences among gastrodermal cells, during development of the larvae. The cells in the larval equator function as nutritive phagocytes, and also appear to function as a region of enhanced symbiont acquisition in F. scutaria.

In pursuit of neural risk factors for weight gain in humans

Obesity is a multifactorial disease associated with an increased risk of type 2 diabetes, coronary artery disease, cancer, and consequently, with a reduced length of life. Metabolic phenotypes of reduced energy expenditure have been associated with weight gain, but their contribution has been estimated to be relatively small. On the other hand, excessive food intake is likely to be the major determinant of positive energy balances and it is underlied by both non-conscious (homeostatic) and conscious (perceptual, emotional, and cognitive) phenomena processed in the brain. Functional neuroimaging is a promising tool to investigate these neural substrates in humans, because it provides a measurement of state-dependent brain regional activity, bridging the gap between neural events and behavioral responses. Using this technology, a few studies have provided the first evidence of functional differences between obese and lean individuals in the brain's response to energy intake and investigated the presence of neural risk factors of weight gain.

Molecular Cloning of Mouse Type 2 and Type 3 Inositol 1,4,5-Trisphosphate Receptors and Identification of a Novel Type 2 Receptor Splice Variant

We isolated cDNAs encoding type 2 and type 3 inositol 1,4,5-trisphosphate (IP(3)) receptors (IP(3)R2 and IP(3)R3, respectively) from mouse lung and found a novel alternative splicing segment, SI(m2), at 176-208 of IP(3)R2. The long form (IP(3)R2 SI(m2)(+)) was dominant, but the short form (IP(3)R2 SI(m2)(-)) was detected in all tissues examined. IP(3)R2 SI(m2)(-) has neither IP(3) binding activity nor Ca(2+) releasing activity. In addition to its reticular distribution, IP(3)R2 SI(m2)(+) is present in the form of clusters in the endoplasmic reticulum of resting COS-7 cells, and after ATP or Ca(2+) ionophore stimulation, most of the IP(3)R2 SI(m2)(+) is in clusters. IP(3)R3 is localized uniformly on the endoplasmic reticulum of resting cells and forms clusters after ATP or Ca(2+) ionophore stimulation. IP(3)R2 SI(m2)(-) does not form clusters in either resting or stimulated cells. IP(3) binding-deficient site-directed mutants of IP(3)R2 SI(m2)(+) and IP(3)R3 fail to form clusters, indicating that IP(3) binding is involved in the cluster formation by these isoforms. Coexpression of IP(3)R2 SI(m2)(-) prevents stimulus-induced IP(3)R clustering, suggesting that IP(3)R2 SI(m2)(-) functions as a negative coordinator of stimulus-induced IP(3)R clustering. Expression of IP(3)R2 SI(m2)(-) in CHO-K1 cells significantly reduced ATP-induced Ca(2+) entry, but not Ca(2+) release, suggesting that the novel splice variant of IP(3)R2 specifically influences the dynamics of the sustained phase of Ca(2+) signals.

Role of the neutrophil in the development of sepsis following abdominal aortic aneurysm surgery

Abstract Background There is evidence to suggest that the neutrophil (PMN) plays a critical early step in development of the ischaemia–reperfusion syndrome and sepsis. Not all patients undergoing aortic aneurysm repair develop these postoperative complications. The PMN receptor CD16 plays an important role in phagocytosis, cell-mediated cytotoxicity and the release of free radicals and proteolytic enzymes. This study determined if there is any relationship between PMN CD16 expression, phagocytosis and the development of sepsis. Methods Some 50 patients (39 men and 11 women, median age 70 years) who underwent elective infrarenal abdominal aortic aneurysm repair were studied. Venous blood was taken before operation, throughout surgery and for 7 days afterwards. CD16 was measured, unstimulated and following further stimulation with phorbol myrisate, lipopolysaccharide and N-formyl-methionyl-leucyl-phenylalanine using flow cytometry. Phagocytosis was measured using flow cytometry and the production of elastase using an enzyme-linked immunosorbent assay. Sepsis was defined according to the ACCP/SCCM definition. Results There were 36 uncomplicated operations and 14 patients with sepsis. There was no difference between the two groups in respect of nutritional, co-morbid or technical factors. In the group that developed septic complications, the level of PMN CD16 expression was significantly higher before operation (30·2 versus 10·4 mcf; P &amp;lt; 0·05, Mann–Whitney U test) and throughout the postoperative period. Surgery produced no change in CD16 expression in either the septic or uncomplicated group. Stimulation of the PMNs before operation caused an increase in CD16 expression in both groups. After operation, stimulation of PMNs in the septic group resulted in a fall in CD16 expression (40·8 versus 20·4 mcf; P &amp;lt; 0·05, Mann–Whitney U test); surgery produced no change in the level of expression in the uncomplicated group. Phagocytic ability was comparable before operation (91·2 versus 94·2 mcf), but showed a greater reduction in the septic group after operation (73·4 versus 86·2 mcf; P &amp;lt; 0·05, Mann–Whitney U test). Elastase concentration was also similar before operation (48 versus 49 μg l−1); after operation, there was a greater increase in the septic group (166 versus 104 μg l−1; P &amp;lt; 0·05, Mann–Whitney U test). Conclusion This study provides evidence of functional differences in PMN behaviour in patients who subsequently develop sepsis following aneurysm surgery. This difference occurs early in the postoperative course and it may be possible to identify these patients before operation.

The herpes simplex virus type 1 Fc receptor discriminates between IgG1 allotypes.

Herpes simplex virus type 1 (HSV-1) expresses a complex of two virally encoded glycoproteins, gE and gl, which is capable of binding nonimmune human IgG. The gE-gl complex has thus become known as an Fc receptor (FcR), which reportedly binds human IgG subclasses in the order IgG4 > IgG1 > or = IgG2 and does not bind IgG3 from many individuals. There is, however, allelic variation in the genes encoding the human IgG1 heavy chain constant region and this gives rise to allotypes of IgG1. Using recombinant monoclonal IgG molecules of known isotype and mutants thereof we have unexpectedly discovered that the HSV-1 FcR discriminates between IgG1 allotypes. This is evidence of functional differences between IgG1 allotypes that may account for their distribution in populations. Furthermore, these findings suggest HSV-1 FcR binding sites on the IgG molecule some distance from the proposed binding site in the CH2-CH3 domain interface.

The herpes simplex virus type 1 Fc receptor discriminates between IgG1 allotypes

Herpes simplex virus type 1 (HSV-1) expresses a complex of two virally encoded glycoproteins, gE and gI, which is capable of binding nonimmune human IgG. The gE-gI complex has thus become known as an Fc receptor (FcR), which reportedly binds human IgG subclasses in the order IgG4 > IgG1 ≥ IgG2 and does not bind IgG3 from many individuals. There is, however, allelic variation in the genes encoding the human IgG1 heavy chain constant region and this gives rise to allotypes of IgG1. Using recombinant monoclonal IgG molecules of known isotype and mutants thereof we have unexpectedly discovered that the HSV-1 FcR discriminates between IgG1 allotypes. This is evidence of functional differences between IgG1 allotypes that may account for their distribution in populations. Furthermore, these findings suggest HSV-1 FcR binding sites on the IgG molecule some distance from the proposed binding site in the CH2-CH3 domain interface.

Trichinella spiralis: Differences between “early” and “late” rapid expulsion evident from inhibition studies using cortisone and irradiation

Cortisone administered once at 100 mg/kg during the first 3 weeks of infection inhibited rapid expulsion. In rats immunized with an abbreviated infection ( T M regime) inhibition averaged approximately 50%, whereas in rats given a complete infection (C.I.) 14% inhibition occurred. Sensitivity to 400 rad whole-body irradiation was greatest 7 days before a challenge infection in all immune rats. Three days after beginning the T M infection rats were highly susceptible to cortisone but only weakly so to irradiation. Rats immunized by C.I. were equally, but only weakly, susceptible to either cortisone or irradiation 3 days after infection. Acute administration of cortisone 1 or 4 hr prior to challenge did not inhibit rapid expulsion but 60% inhibition occurred when cortisone was given 24 hr prior to challenge. Inhibition of rapid expulsion by irradiation 7 days prior to challenge was not reversed by immune serum and irradiation did not affect antibody titer in treated rats. It was suggested that irradiation 7 days before challenge compromised the intestinal, and not the immunological, component of rapid expulsion. Differences in sensitivity of “early” and “late” rapid expulsion to irradiation and cortisone therapy provide further evidence of functional differences between these rejection processes.

Comparison of spontaneous loss of catecholamines and ATP in vitro from isolated bovine adrenomedullary, vesicular gland, vas deferens and splenic nerve granules.

SUMMARYThe molar ratio catecholamines/ATP in the high speed sediment from homogenates of bovine adrenal medulla, vesicular gland, vas deferens and splenic nerve was relatively close to the‘equivalence ratio’of 4/1. On incubation in vitro the loss of amines and ATP from the medullary granules was slow and largely parallel. Thus the original amine/ATP ratio was maintained. The amine loss from the nerve granules occurred at a very high, and from the vesicular gland and vas deferens granules at an intermediate, rate. On the other hand, the decrease in ATP in these preparations was quite slow, leading to a marked change in the original amine/ATP ratio. These findings are regarded as further evidence of functional differences between granules derived from chromaffin cells and from sympathetic nerve tissue, and even between nerve granules from‘long’and 'short’noradrenergic neurons. The possible implications of these in vitro differences in amine and ATP release are discussed in relation to the mechanisms of amine release in vivo.