Citrullination, a possible functional link between susceptibility genes and rheumatoid arthritis

Antibodies directed to citrullinated proteins (anti-cyclic citrullinated peptide) are highly specific for rheumatoid arthritis (RA). Recent data suggest that the antibodies may be involved in the disease process of RA and that several RA-associated genetic factors might be functionally linked to RA via modulation of the production of anti-cyclic citrullinated peptide antibodies or citrullinated antigens.     

Development and maintenance of a B220- memory B cell compartment

We have recently demonstrated that a novel somatically mutated B220(-) memory B cell subset rapidly dominates the secondary immune response to (4-hydroxy-3-nitrophenyl) acetyl (NP). Upon adoptive transfer with Ag, B220(+)NP(+) memory B cells produce large numbers of B220(-)NP(+) B cells that can rapidly differentiate into plasma cells. Therefore, it is not clear whether the novel B220(-) memory compartment is a consequence of secondary Ag challenge or whether it develops as a stable memory subset after initial Ag challenge. In this study, we demonstrate the gradual emergence of B220(-)NP(+) B cells in the spleen to maximal numbers 3 wk after initial Ag exposure. Like their B220(+) counterparts, the B220(-) B cells initially appear unmutated at days 5-7; however, the majority rapidly accumulate affinity increasing mutations by days 9-14 of the primary immune response. More extensive cell surface phenotype (GL7(-)BLA-1(-)CD24(-)CD43(+)) argues strongly against germinal center localization and direct analysis in situ places a cohort of B220(-)CD11b(+)NP(+) B cells in the red pulp of the spleen and not in the MZs. These data provide direct evidence for the development of B220(-) memory B cells as a unique cellular consequence of primary Ag exposure. The cellular dynamics and molecular attributes of these unique memory B cells suggest they are distinct cellular products of the germinal center reaction in the primary response and are maintained long-term in the spleen and bone marrow.     

Top-down modulation of lateral interactions in early vision: does attention affect integration of the whole or just perception of the parts?

Attention can modulate sensitivity to local stimuli in early vision. But, can attention also modulate integration of local stimuli into global visual patterns? We recently measured effects of attention on the phenomenon of lateral interactions between collinear elements, commonly thought to reflect long-range mechanisms in early visual cortex underlying contour integration. We showed improved detection of low-contrast central Gabor targets in the context of collinear flankers, but only when the collinear flankers were attended for a secondary task rather than ignored in favor of an orthogonal flanker pair. Here, we contrast two hypotheses for how attention might modulate flanker influences on the target: by changing just local sensitivity to the flankers themselves (flanker-modulation-only hypothesis), or by weighting integrative connections between flanker and target (connection-weighting hypothesis). Modeled on the known nonlinear dependence of target visibility on collinear flanker contrast, the first hypothesis predicts that an increase in physical flanker contrast should readily offset any reduction in their effective contrast when ignored, thus eliminating attentional modulation. Conversely, the second hypothesis predicts that attentional modulation should persist even for the highest flanker contrasts. Our results showed the latter outcome and indicated that attention modulates flanker-target integration, rather than just processing of local flanker elements.     

Crossmodal spatial influences of touch on extrastriate visual areas take current gaze direction into account

Recent results indicate that crossmodal interactions can affect activity in cortical regions traditionally regarded as "unimodal." Previously we found that combining touch on one hand with visual stimulation in the anatomically corresponding hemifield could boost responses in contralateral visual cortex. Here we manipulated which visual hemifield corresponded to the location of the stimulated hand, by changing gaze direction such that right-hand touch could now arise in either the left or right visual field. Crossmodal effects on visual cortex switched from one hemisphere to the other, depending on gaze direction, regardless of whether the hand was seen. This indicates that crossmodal influences of touch upon visual cortex depend on spatial alignment for the multimodal stimuli, with gaze posture taken into account.     

Phylogenetic relationships of world populations of Bemisia tabaci (Gennadius) using ribosomal ITS1

A phylogeny of Bemisia tabaci is presented based on the ITS1 region of ribosomal DNA. The monophyly of each biotype of Bemisia is supported, and a strong biogeographic pattern is evident in the data. Populations from the Americas (including the A biotype) form a clade sister to a clade comprising the silverleafing or B biotype and a nonsilverleafing biotype from the North Africa/Mediterranean region. Polymorphisms in rDNA suggest that silverleafing is a recent phenomenon, while the nonsilverleafing form is the ancestral or plesiomorphic state. Based on this phylogeny, if B. argentifolii is accepted as a separate species then one would have to review the taxonomic status of all biotypes of B. tabaci. In particular, a new name clearly would be needed for an Egypt/Spain/Sudan/Nigeria clade, and the monophyly of the haplotypes remaining in B. tabaci would be open to serious doubt. To make new species assignments in these circumstances seems premature. The phylogenetic relationships of the different populations of B. tabaci and the origins of effective natural enemies of the B biotype suggest that knowing the origin of the B biotype is not essential to finding effective agents and supports the notion that crop management is the key aspect to control.     

Modulation of visual processing by attention and emotion: windows on causal interactions between human brain regions

Visual processing is not determined solely by retinal inputs. Attentional modulation can arise when the internal attentional state (current task) of the observer alters visual processing of the same stimuli. This can influence visual cortex, boosting neural responses to an attended stimulus. Emotional modulation can also arise, when affective properties (emotional significance) of stimuli, rather than their strictly visual properties, influence processing. This too can boost responses in visual cortex, as for fear-associated stimuli. Both attentional and emotional modulation of visual processing may reflect distant influences upon visual cortex, exerted by brain structures outside the visual system per se. Hence, these modulations may provide windows onto causal interactions between distant but interconnected brain regions. We review recent evidence, noting both similarities and differences between attentional and emotional modulation. Both can affect visual cortex, but can reflect influences from different regions, such as fronto-parietal circuits versus the amygdala. Recent work on this has developed new approaches for studying causal influences between human brain regions that may be useful in other cognitive domains. The new methods include application of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) measures in brain-damaged patients to study distant functional impacts of their focal lesions, and use of transcranial magnetic stimulation concurrently with fMRI or EEG in the normal brain. Cognitive neuroscience is now moving beyond considering the putative functions of particular brain regions, as if each operated in isolation, to consider, instead, how distinct brain regions (such as visual cortex, parietal or frontal regions, or amygdala) may mutually influence each other in a causal manner.