Microcephaly: general considerations and aids to nosology

Microcephaly is defined as an occipito-frontal head circumference (OFC) 2 or more standard deviations below the mean for age and sex using the new Roche et al. [Pediatrics 1987;79:706-712] charts, and corrected for parental OFC by the method of Weaver and Christian [J Pediatr 1980;96:990-994]. "Relative" microcephaly, i.e., a small head on a small child, may be associated with a much better intellectual prognosis than absolute microcephaly, although the average IQ of children with absolute microcephaly ascertained in a normal school system is normal when compared with that of appropriate control children. "Primary" microcephaly means an abnormal OFC at birth (corrected for gestational age and length), and "secondary" microcephaly a normal birth OFC with later, acquired microcephaly due to deceleration of brain growth reflecting infection, trauma, intoxication, metabolic disease, the Rett syndrome, or a true CNS degenerative disease. Some cases of syndromal microcephaly may be associated with normal intelligence including some "primordial dwarfs," children with Dubowitz syndrome, FAS, mild SC-Roberts syndrome, and an occasional Brachmann-de Lange individual. The nosology of (syndromal) microcephaly is extraordinarily complex and requires the assistance of special library resources and information retrieval expertise. At a minimum, it requires McKusick's Catalog of Mendelian Inheritance in Man (MIM); however, we find that our work is greatly enhanced by recently developed electronic databases such as MIM-online (OMIM), POSSUM, SYNDROME, and MEDLINE, as well. Three groups of syndromal and non-syndromal microcephaly are discussed selectively in order to illustrate the marvels of pleiotropy in human development and its abnormalities and the difficulties encountered in splitting and lumping entities with overlapping manifestations.     

Distinct Contributions of the Dorsolateral Prefrontal and Orbitofrontal Cortex during Emotion Regulation

The lateral prefrontal and orbitofrontal cortices have both been implicated in emotion regulation, but their distinct roles in regulation of negative emotion remain poorly understood. To address this issue we enrolled 58 participants in an fMRI study in which participants were instructed to reappraise both negative and neutral stimuli. This design allowed us to separately study activations reflecting cognitive processes associated with reappraisal in general and activations specifically related to reappraisal of negative emotion. Our results confirmed that both the dorsolateral prefrontal cortex (DLPFC) and the lateral orbitofrontal cortex (OFC) contribute to emotion regulation through reappraisal. However, activity in the DLPFC was related to reappraisal independently of whether negative or neutral stimuli were reappraised, whereas the lateral OFC was uniquely related to reappraisal of negative stimuli. We suggest that relative to the lateral OFC, the DLPFC serves a more general role in emotion regulation, perhaps by reflecting the cognitive demand that is inherent to the regulation task.     

Different time courses for learning-related changes in amygdala and orbitofrontal cortex

The orbitofrontal cortex (OFC) and amygdala are thought to participate in reversal learning, a process in which cue-outcome associations are switched. However, current theories disagree on whether OFC directs reversal learning in the amygdala. Here, we show that during reversal of cues' associations with rewarding and aversive outcomes, neurons that respond preferentially to stimuli predicting aversive events update more quickly in amygdala than OFC; meanwhile, OFC neurons that respond preferentially to reward-predicting stimuli update more quickly than those in the amygdala. After learning, however, OFC consistently differentiates between impending reinforcements with?a shorter latency than the amygdala. Finally, analysis of local field potentials (LFPs) reveals a disproportionate influence of OFC on amygdala that emerges after learning. We propose that reversal learning is supported by complex interactions between neural circuits spanning the amygdala and OFC, rather than directed by any single structure.     

大鼠眶额叶皮质受损破坏新异性探索行为

利用旷场测试和Y-迷宫测试两种行为模型检测了双侧眶额叶（orbitofrontal cortex, OFC）电损伤或假损伤雄性SD大鼠的新异性探索行为, 探讨了OFC在大鼠探索新异环境中的作用。旷场测试的结果发现,OFC损伤大鼠的行走距离和直立次数较假损组有明显降低;同时,在Y-迷宫测试中与假损伤组大鼠相比,OFC损伤大鼠在新异臂的访问时间和穿梭次数明显降低。提示眶额叶皮质在大鼠新异性探索行为中起着重要作用。     

Effects of the removal of the orbito-frontal cortex on the development of reflex analgesia

The authors studied the effect of electric acupuncture stimulation (EAP) on the changes in pain thresholds prior to and after removal of the orbito-frontal cortex (OFC) of the brain in behavioral experiments on adult cats. Removal of OFC increased the thresholds of pain response at the 4th and the 5th levels of the conventional scale, reflecting emotionally-affective manifestations of pain, and intensified the effect of antinociceptive EAP. The results obtained are analysed in relation to the inhibitory tonic effect of OFC on antinociceptive structures of the brain. Different effects of OFC and somatosensory cortex on the antinociceptive structures of the brain are discussed.     

Representation of spatial goals in rat orbitofrontal cortex

The orbitofrontal cortex (OFC) is thought to participate in making and evaluating goal-directed decisions. In rodents, spatial navigation is a major mode of goal-directed behavior, and anatomical and lesion studies implicate the OFC in spatial processing, but there is little direct evidence for coding of spatial or motor variables. Here, we recorded from ventrolateral and lateral OFC in an odor-cued two-alternative choice task requiring orientation and approach to spatial goal ports. In this context, over half of OFC neurons encoded choice direction or goal port location. A subset of neurons was jointly selective for the trial outcome and port location, information useful for the selection or evaluation of spatial goals. These observations show that the rodent OFC not only encodes information relating to general motivational significance, as shown previously, but also encodes spatiomotor variables needed to define specific behavioral goals and the locomotor actions required to attain them.     

Altered Fronto-Striatal Fiber Topography and Connectivity in Obsessive-Compulsive Disorder

Fronto-striatal circuits are hypothesized to be involved in the pathophysiology of obsessive-compulsive disorder (OCD). Within this circuitry, ventral frontal regions project fibers to the ventral striatum (VS) and dorsal frontal regions to the dorsal striatum. Resting state fMRI research has shown higher functional connectivity between the orbitofrontal cortex (OFC) and the dorsal part of the VS in OCD patients compared to healthy controls (HC). Therefore, we hypothesized that in OCD the OFC predominantly project fibers to the more dorsal part of the VS, and that the structural connectivity between the OFC and VS is higher compared to HC. A total of 20 non-medicated OCD patients and 20 HC underwent diffusion-weighted imaging. Connectivity-based parcellation analyses were performed with the striatum as seed region and the OFC, dorsolateral prefrontal cortex, and dorsal anterior cingulate cortex as target regions. Obtained connectivity maps for each frontal region of interest (ROI) were normalized into standard space, and Z-component (dorsal–ventral) coordinate of center-of-gravity (COG) were compared between two groups. Probabilistic tractography was performed to investigate diffusion indices of fibers between the striatum and frontal ROIs. COG Z-component coordinates of connectivity maps for OFC ROI were located in the more dorsal part of the VS in OCD patients compared to HC. Fractional anisotropy of fibers between the OFC and the striatum was higher in OCD patients compared to HC. Part of the pathophysiology of OCD might be understood by altered topography and structural connectivity of fibers between the OFC and the striatum.     

Human processing of behaviorally relevant and irrelevant absence of expected rewards: a high-resolution ERP study

Acute lesions of the posterior medial orbitofrontal cortex (OFC) in humans may induce a state of reality confusion marked by confabulation, disorientation, and currently inappropriate actions. This clinical state is strongly associated with an inability to abandon previously valid anticipations, that is, extinction capacity. In healthy subjects, the filtering of memories according to their relation with ongoing reality is associated with activity in posterior medial OFC (area 13) and electrophysiologically expressed at 220-300 ms. These observations indicate that the human OFC also functions as a generic reality monitoring system. For this function, it is presumably more important for the OFC to evaluate the current behavioral appropriateness of anticipations rather than their hedonic value. In the present study, we put this hypothesis to the test. Participants performed a reversal learning task with intermittent absence of reward delivery. High-density evoked potential analysis showed that the omission of expected reward induced a specific electrocortical response in trials signaling the necessity to abandon the hitherto reward predicting choice, but not when omission of reward had no such connotation. This processing difference occurred at 200-300 ms. Source estimation using inverse solution analysis indicated that it emanated from the posterior medial OFC. We suggest that the human brain uses this signal from the OFC to keep thought and behavior in phase with reality.     

Converting human skin cells to neurons: a new tool to study and treat brain disorders?

Recent publications in Cell Stem Cell (Son et?al., 2011; Ambasudhan et?al., 2011), PNAS (Pfisterer et?al., 2011), and Nature (Caiazzo et?al., 2011; Pang et?al., 2011; Yoo et?al., 2011) report that functional neurons can be directly generated from human fibroblast cells without going through the pluripotent state.     

Re-evaluation of phytohormone-independent division of tobacco protoplast-derived cells

We have used a [³H] thymidine incorporation assay and microscopic observation in order to reassess recently published data dealing with the response of tobacco protoplasts to phytohormones, lipochitooligosaccharides and peptides ( Harling et al . 1997 ; Hayashi et al . 1992 ; Miklashevichs et al . 1996 ; Miklashevichs et al . 1997 ; Röhrig et al . 1995 ; Röhrig et al . 1996 ; van de Sande et al . 1996 ; Walden et al . 1994 ). These proliferation assays reveal that, in contrast to published data, isolated cells of the investigated mutant plant lines axi159 ( Hayashi et al . 1992 ; Walden et al . 1994 ), axi4/1 ( Harling et al . 1997 ) and cyi1 ( Miklashevichs et al . 1997 ), which were generated by activation T-DNA tagging, were unable to grow in the absence of auxin or cytokinin. Furthermore, lipochitooligosaccharides which play a key role in the induction of nodules on roots of legumes were unable to promote auxin- or cytokinin-independent cell division in tobacco protoplasts as claimed by Röhrig et al . (1995 , 1996 ). The finding of van de Sande et al . (1996 ) that ENOD40 confers tolerance of high auxin concentration to wild-type tobacco protoplasts was also reinvestigated. The results of our investigations show that we were unable to reproduce the proliferation data presented in this study, which were obtained by counting tobacco protoplast-derived cells undergoing division. In total, none of the published data on phytohormone-independent division of tobacco cells could be reproduced.     

The aging human orbitofrontal cortex: decreasing polyunsaturated fatty acid composition and associated increases in lipogenic gene expression and stearoyl-CoA desaturase activity

Orbitofrontal cortex (OFC, Brodmann area 10) gray matter volume reductions and selective reductions in docosahexaenoic acid (DHA, 22:6n-3) are observed in adult patients with major depressive disorder (MDD). OFC gray matter volume also decreases with advancing age in healthy subjects. To examine if OFC gray matter DHA composition decreases during normal aging, we determined age-related changes in OFC gray matter fatty acid composition by gas chromatography in subjects aged 29-80 years (n=30). We additionally determined elongase (HELO1), delta-5 desaturase (FASD1), delta-6 desaturase (FASD2), peroxisomal (PEX19), and stearoyl-CoA desaturase (SCD) mRNA expression in the same tissues. Increasing age was associated with a progressive decline in polyunsaturated fatty acid (PUFA) composition, including DHA and arachidonic acid (AA, 20:4n-6), and transient, apparently compensatory, elevations in elongase and desaturase gene expression. The age-related reduction in PUFA composition was inversely correlated with SCD expression and activity resulting in elevations in monounsaturated fatty acid composition. These dynamic age-related changes in OFC gray matter fatty acid composition and biosynthetic gene expression may contribute to the progressive decline in OFC gray matter volume found with advancing age. The implications of age-related reductions in OFC PUFA composition for affective dysregulation in the elderly are discussed.     

Basolateral amygdala lesions abolish orbitofrontal-dependent reversal impairments

Damage to orbitofrontal cortex (OFC) has long been associated with deficits in reversal learning. OFC damage also causes inflexible associative encoding in basolateral amygdala (ABL) during reversal learning. Here we provide a critical test of the hypothesis that the reversal deficit in OFC-lesioned rats is caused by this inflexible encoding in ABL. Rats with bilateral neurotoxic lesions of OFC, ABL, or both areas were tested on a series of two-odor go/no-go discrimination problems, followed by two serial reversals of the final problem. As expected, all groups acquired the initial problems at the same rate, and rats with OFC lesions were slower to acquire the reversals than sham controls. This impairment was abolished by accompanying ABL lesions, while ABL lesions alone had no effect on reversal learning. These results are consistent with the hypothesis that OFC facilitates cognitive flexibility by promoting updating of associative encoding in downstream brain areas.     

New Phytologist 140 (1998), 363–383

In the November 1998 issue of New Phytologist , we published the Tansley review 'Gibberellins: regulating genes and germination' by Sian Ritchie and Simon Gilroy ( New Phytol. (1998) 140 , 363–383). Since its publication, it has come to our attention that text associated with Fig. 4 was omitted during production. The correct figure is reprinted here in full.
We apologise to the author and to our readers for this mistake.
Figure 4. Promoter sequences of various genes expressed in the cereal aleurone and shown to be regulated by GA. The position of each sequence is indicated relative to the start codon. Regions identified as being involved in regulation of the genes are highlighted, as are similar regions in other genes. Sites at which protein has been shown to bind are also indicated. ( a ) Barley Amy 32b (Sutcliff et al ., 1993; Whittier et al ., 1987); wheat Amy 2/54 (Huttley et al ., 1992; Rushton et al ., 1992; Rushton et al ., 1995); barley Amy 46 (Khursheed & Rogers, 1988); barley Amy 2/p155 (Knox et al ., 1987); barley aleurain (Whittier et al ., 1987); barley β-glucanase II (Wolf, 1992); wheat cathepsin B-like (Cejudo et al ., 1992); rice ubiquitin-conjugating enzyme (Chen et al ., 1995). ( b ). Wheat Amy 1/18 (Rushton et al ., 1992); barley Amy pHV 19 (Jacobsen & Close, 1991; Gubler & Jacobsen, 1992)/ Amy 1 / 6-4 (Khursheed & Rogers, 1988; Rogers, Lanahan & Rogers 1994); rice OSamy-a / Amy 3c (Ou-Lee et al ., 1988; Sutcliff et al ., 1991; Yu et al ., 1992; Goldman et al ., 1994); rice Amy 3B (Sutcliffe et al ., 1991); rice OSamy-c (Kim et al ., 1992; Kim & Wu, 1992; Tanida et al ., 1994); rice Amy 1A (Huang et al ., 1990; Itoh et al ., 1995).
Figure 4 ( b ). For legend see facing page.     

Neuronal representations of stimuli in the mouth: the primate insular taste cortex, orbitofrontal cortex and amygdala

The responses of 3687 neurons in the macaque primary taste cortex in the insula/frontal operculum, orbitofrontal cortex (OFC) and amygdala to oral sensory stimuli reveals principles of representation in these areas. Information about the taste, texture of what is in the mouth (viscosity, fat texture and grittiness, which reflect somatosensory inputs), temperature and capsaicin is represented in all three areas. In the primary taste cortex, taste and viscosity are more likely to activate different neurons, with more convergence onto single neurons particularly in the OFC and amygdala. The different responses of different OFC neurons to different combinations of these oral sensory stimuli potentially provides a basis for different behavioral responses. Consistently, the mean correlations between the representations of the different stimuli provided by the population of OFC neurons were lower (0.71) than for the insula (0.81) and amygdala (0.89). Further, the encoding was more sparse in the OFC (0.67) than in the insula (0.74) and amygdala (0.79). The insular neurons did not respond to olfactory and visual stimuli, with convergence occurring in the OFC and amygdala. Human psychophysics showed that the sensory spaces revealed by multidimensional scaling were similar to those provided by the neurons.     

Carbon and water fluxes in ecologically vulnerable areas in China

Ecologic vulnerable areas (EVAs) are the regions where ecosystems are fragile and vulnerable to suffer from degradation with external disturbances, e.g. environmental changes and human activities (Feng et al. 2022; Wang et al. 2019). EVAs in China are widely distributed and account for more than 55% China’s land area (Ministry of Ecology and Environment of the People’s Republic of China 2008). The ecosystem in EVAs, chartered with low stability, weak resistance and high vulnerability, has been experiencing significant degradation owing to the impacts of global climate change and human activities (Bai et al. 2018; Chen et al. 2021; Yu et al. 2022). The EVAs in China are not only the most serious areas of environmental degradation, but also the most poverty-stricken regions (Wang et al. 2019). Harsh environmental condition (drought, low temperature and strong radiation) and limited resource supply (water, soil nutrients, etc.) constrain the vegetation productivity and ecosystem services of EVAs (Li et al. 2021). Climate change adds new challenges with warmer temperatures, changing rainfall regime and increasing frequency of extreme events (drought, heat wave, storms, etc.), which make it is more difficult to predict the changes of ecosystem processes and functions in future scenarios (Piao et al. 2020; Reid et al. 2014). Carbon and water fluxes are the core ecosystem processes, which is linked to diverse ecosystem services (Lian et al. 2021). Therefore, clarifying the variations and controls of ecosystem carbon and water fluxes is an effective approach to clarifying how ecosystem respond to global change in EVAs (Baldocchi 2020). As the only technique can directly measure the carbon, water and energy fluxes between vegetation and atmosphere, eddy covariance technique has been considered as a standard method for flux observations (Chen et al. 2020). By integrating long-term, eddy covariance measurements over time and space, researches are able to assess ecosystem metabolism at different time scales (hours to decades) (Forzieri et al. 2020; Han et al. 2020; Jung et al. 2017). Eddy covariance measurements also produce information on how ecosystem respond to the changes in climate, which is useful for assessing ecosystem carbon sequestration (Hu et al. 2018), water and energy balance (Forzieri et al. 2020), resource use efficiency (Liu et al. 2019) and ecosystem feedback to climate change (Huang et al. 2019; Piao et al. 2020; Yue et al. 2020). Long-term flux measurements are also vital for detecting the responses of ecosystem functions to extreme events, optimizing and validating models on regional and global scales (Baldocchi 2020). Combining with remote sensing and ecosystem modeling techniques, scientists can upscale and evaluate the functional relations between carbon and water fluxes with environmental variables at high resolution and across diverse spatial/temporal scales (Niu et al. 2017; Xia et al. 2020).     

Sinoatrial node pacemaker cells:cardiomyocyte-or neuron-like cells?

The sinoatrial node(SAN)is the headquarter of heartbeat throughout our lifetime(Lakatta et al.,2010;Cingolani et al.,2018;Peters et al.,2020).Every beat of the heart is triggered by a bioelectric pulse spontaneously released by SAN pacemaker cells(SANPCs)(Yaniv et al.,2014;Yavari et al.,2017).In adult human heart,the SAN is a crescent-shaped structure of 1-2 cm long and 0.5 cm wide,which is located at the junction of the superior vena cava and the right atrium and lies along the sulcus terminalis(John et al.,2016).However,the nature of SANPCs remains incompletely known.In general,SANPCs have long been considered as specialized cardiomyocytes(Van Eif et al.,2018;Linscheid et al.,2019;Galang et al.,2020;).However,SANPCs do not have myofibril and T-tube,thus not sharing the contractility property of cardiomyocytes(Satoh,2003;Protze et al.,2017).Interestingly,SANPCs share some electrophysiolog-ical characteristics with neurons:excitability and conductiv-ity.In addition,SANPCs have their intrinsic autonomic rhythm,while neurons also possess the intrinsic ability to generate spontaneous electrical impulses(Lisman et al.,2018).Whether SANPCs are neuron-like cells that reside in the heart remains enigmatic in the field.     

Epigenetic Variations in Plant Hybrids and Their Potential Roles in Heterosis

Heterosis,one of the most important biological phenomena,refers to the phenotypic superiority of a hybrid over its genetically diverse parents with respect to many traits such as biomass,growth rate and yield.Despite its successful application in breeding and agronomic production of many crop and animal varieties,the molecular basis of heterosis remains elusive.The classic genetic explanations for heterosis centered on three hypotheses:dominance (Davenport,1908;Bruce,1910;Keeble and Pellew,1910;Jones,1917),overdominance (East,1908;Shull,1908) and epistasis (Powers,1944;Yu et al.,1997).However,these hypotheses are largely conceptual and not connected to molecular principles,and are therefore insufficient to explain the molecular basis of heterosis (Birchler et al.,2003).Recently,many studies have explored the molecular mechanism of heterosis in plants at a genome-wide level.These studies suggest that global differential gene expression between hybrids and parental lines potentially contributes to heterosis in plants (e.g.,Swanson-Wagner et al.,2006;Zhang et al.,2008;Wei et al.,2009;Song et al.,2010).Research suggests that genetic components,including cis-acting elements and trans-acting factors,are critical regulators of differential gene expression in hybrids (Hochholdinger and Hoecker,2007;Springer and Stupar,2007;Zhang et al.,2008).However,other research indicates that epigenetic components,the regulators of chromatin states and genome activity,also have the potential to impact heterosis (e.g.,Ha et al.,2009;He et al.,2010;Groszmann et al.,2011;Barber et al.,2012;Chodavarapu et al.,2012;Greaves et al.,2012a;Shen et al.,2012).