Corticospinal tract asymmetry and handedness in right- and left-handers by diffusion tensor tractography

Purpose

Cerebral hemispheres represent both structural and functional asymmetry, which differs among right- and left-handers. The left hemisphere is specialised for language and task execution of the right hand in right-handers. We studied the corticospinal tract in right- and left-handers by diffusion tensor imaging and tractography. The present study aimed at revealing a morphological difference resulting from a region of interest (ROI) obtained by functional MRI (fMRI).

Methods

Twenty-five healthy participants (right-handed: 15, left-handed: 10) were enrolled in our assessment of morphological, functional and diffusion tensor MRI. Assessment of brain fibre reconstruction (tractography) was done using a deterministic algorithm. Fractional anisotropy (FA) and mean diffusivity (MD) were studied on the tractography traces of the reference slices.

Results

We observed a significant difference in number of leftward fibres based on laterality. The significant difference in regard to FA and MD was based on the slices obtained at different levels and the laterality index. We found left-hand asymmetry and right-hand asymmetry, respectively, for the MD and FA.

Conclusions

Our study showed the presence of hemispheric asymmetry based on laterality index in right- and left-handers. These results are inconsistent with some studies and consistent with others. The reported difference in hemispheric asymmetry could be related to dexterity (manual skill).     

Complex karyotype in mantle cell lymphoma is a strong prognostic factor for the time to treatment and overall survival,independent of the MCL international prognostic index

Mantle cell lymphoma (MCL) is usually an aggressive disease. However, a few patients do have an “indolent” evolution (iMCL) defined by a long survival time without intensive therapy. Many studies highlight the prognostic role of additional genetic abnormalities, but these abnormalities are not routinely tested for and do not yet influence the treatment decision. We aimed to evaluate the prognostic impact of these additional abnormalities detected by conventional cytogenetic testing, as well as their relationships with the clinical characteristics and their value in identifying iMCL. All consecutive MCL cases diagnosed between 1995 and 2011 at four institutions were retrospectively selected on the basis of an informative karyotype with a t(11;14) translocation at the time of diagnosis. A total of 125 patients were included and followed for an actual median time of 35 months. The median overall survival (OS) and survival without treatment (TFS) were 73.7 and 1.3 months, respectively. In multivariable Cox models, a high mantle cell lymphoma international prognostic index score, a complex karyotype, and blastoid morphology were independently associated with a shortened OS. Spleen enlargement, nodal presentation, extra‐hematological involvement, and complex karyotypes were associated with shorter TFS. A score based on these factors allowed for the identification of “indolent” patients (median TFS 107 months) from other patients (median TFS: 1 month). In conclusion, in this multicentric cohort of MCL patients, a complex karyotype was associated with a shorter survival time and allowed for the identification of iMCL at the time of diagnosis. © 2013 Wiley Periodicals, Inc.     

Neural representations of ethologically relevant hand/mouth synergies in the human precentral gyrus

Complex motor responses are often thought to result from the combination of elemental movements represented at different neural sites. However, in monkeys, evidence indicates that some behaviors with critical ethological value, such as self-feeding, are represented as motor primitives in the precentral gyrus (PrG). In humans, such primitives have not yet been described. This could reflect well-known interspecies differences in the organization of sensorimotor regions (including PrG) or the difficulty of identifying complex neural representations in peroperative settings. To settle this alternative, we focused on the neural bases of hand/mouth synergies, a prominent example of human behavior with high ethological value. By recording motor- and somatosensory-evoked potentials in the PrG of patients undergoing brain surgery (2–60 y), we show that two complex nested neural representations can mediate hand/mouth actions within this structure: (i) a motor representation, resembling self-feeding, where electrical stimulation causes the closing hand to approach the opening mouth, and (ii) a motor–sensory representation, likely associated with perioral exploration, where cross-signal integration is accomplished at a cortical site that generates hand/arm actions while receiving mouth sensory inputs. The first finding extends to humans’ previous observations in monkeys. The second provides evidence that complex neural representations also exist for perioral exploration, a finely tuned skill requiring the combination of motor and sensory signals within a common control loop. These representations likely underlie the ability of human children and newborns to accurately produce coordinated hand/mouth movements, in an otherwise general context of motor immaturity.Since Penfield’s original work, it is commonly assumed that complex motor responses are produced by combining elemental movements that are independently represented at different neural sites (1). However, the generality of this model was recently challenged in nonhuman primates, where reaching, grasping, defensive, and hand/mouth movements have been found to be represented as complex motor primitives in independent circumscribed territories of the precentral gyrus (PrG) (2–4). To account for this observation, it was suggested that complex motor primitives have emerged during primate evolution to optimize the production of ethologically relevant behaviors (4). However, to date, direct evidence is lacking that such integrated representations of ethologically relevant movements also exist in humans. This may have two different origins.First, it could be that complex ethologically relevant representations exist in human PrG but have not yet been described, due to the difficulty of identifying neural representations associated with the expression of elaborate sensorimotor behaviors in peroperative contexts. With respect to this point, Penfield and other researchers have clearly reported complex multijoint motor responses following cortical stimulation (5–8), including concurrent movements of the hand and mouth (9). Nevertheless, these movements were not investigated systematically in several subjects, described in detail, or related to the existence of integrated neural representations for ethologically relevant behaviors. An obstacle to the investigation of these representations could have been the tendency to stop the stimulation following movement onset. This was explicitly acknowledged by Penfield in the following terms: “the stimulating electrode has frequently been removed at the first evidence of response, and thus the opportunity of producing more of the elaborate synergic responses may have been missed” (6).At a second level, it could be that the PrG does not contain functional representations of complex ethologically relevant behaviors in humans. This possibility is consistent with the existence of substantial dissimilarities in sensorimotor organization between human and nonhuman primates (10, 11). Interestingly, these dissimilarities are well documented for the precentral region mediating ethological synergies in monkeys. In this species, electrical stimulation in the rostral part of PrG evokes coordinated hand-to-mouth movements (12). These movements are part of the behavioral repertoire of the primate newborns (13), which is consistent with the observation that the rostral (phylogenetically oldest) part of PrG lacks cortico-motoneural cells and generates movements by recruiting the integrative mechanisms of the spinal cord through descending projections that are mature at birth (14). However, in human infants, the difficulty of evoking motor responses through electrical stimulation of the rostral PrG does not seem consistent with the existence of early mature descending projections (15, 16). Also, in adults, transcranial magnetic stimulation studies have suggested, in apparent contrast with monkey data, that late-maturing cortico-motoneural cells are present in the human rostral PrG (17, 18).The main aim of this study was to determine whether integrated neural representations of complex actions can be found in the human PrG. We investigated this possibility by studying the neural bases of hand/mouth synergies, a salient example of early and elaborate human behavior with high ethological value (19–21). To this end, motor and somatosensory mapping were combined in children and adult patients undergoing brain surgeries.     

Inactivation of AMPKα1 induces asthenozoospermia and alters spermatozoa morphology

AMP-activated protein kinase (AMPK), a key regulator of cellular energy homeostasis, is present in metabolic tissues (muscle and liver) and has been identified as a modulator of the female reproductive functions. However, its function in the testis has not yet been clearly defined. We have investigated the potential role of AMPK in male reproduction by using transgenic mice lacking the activity of AMPK catalytic subunit α1 gene [α1AMPK knockout (KO)]. In the testis, the α1AMPK subunit is expressed in germ cells and also in somatic cells (Sertoli and Leydig cells). α1AMPK KO male mice show a decrease in fertility, despite no clear alteration in the testis morphology or sperm production. However, in α1AMPK(-/-) mice, we demonstrate that spermatozoa have structural abnormalities and are less motile than in control mice. These spermatozoa alterations are associated with a 50% decrease in mitochondrial activity, a 60% decrease in basal oxygen consumption, and morphological defects. The α1AMPK KO male mice had high androgen levels associated with a 5- and 3-fold increase in intratesticular cholesterol and testosterone concentrations, respectively. High concentrations of proteins involved in steroid production (3β-hydroxysteroid dehydrogenase, cytochrome steroid 17 alpha-hydroxylase/17,20 lysate, and steroidogenic acute regulatory protein) were also detected in α1AMPK(-/-) testes. In the pituitary, the LH and FSH concentrations tended to be lower in α1AMPK(-/-) male mice, probably due to the negative feedback of the high testosterone levels. These results suggest that total α1AMPK deficiency in male mice affects androgen production and quality of spermatozoa, leading to a decrease in fertility.     

TWIK1, a unique background channel with variable ion selectivity

TWIK1 belongs to the family of background K(+) channels with two pore domains. In native and transfected cells, TWIK1 is detected mainly in recycling endosomes. In principal cells in the kidney, TWIK1 gene inactivation leads to the loss of a nonselective cationic conductance, an unexpected effect that was attributed to adaptive regulation of other channels. Here, we show that TWIK1 ion selectivity is modulated by extracellular pH. Although TWIK1 is K(+) selective at neutral pH, it becomes permeable to Na(+) at the acidic pH found in endosomes. Selectivity recovery is slow after restoration of a neutral pH. Such hysteresis makes plausible a role of TWIK1 as a background channel in which selectivity and resulting inhibitory or excitatory influences on cell excitability rely on its recycling rate between internal acidic stores and the plasma membrane. TWIK1(-/-) pancreatic β cells are more polarized than control cells, confirming a depolarizing role of TWIK1 in kidney and pancreatic cells.     

Bacteriophage T4 polynucleotide kinase triggers degradation of mRNAs

The bacteriophage T4-encoded RegB endoribonuclease is produced during the early stage of phage development and targets mostly (but not exclusively) the Shine-Dalgarno sequences of early genes. In this work, we show that the degradation of RegB-cleaved mRNAs depends on a functional T4 polynucleotide kinase/phosphatase (PNK). The 5'-OH produced by RegB cleavage is phosphorylated by the kinase activity of PNK. This modification allows host RNases G and E, with activity that is strongly stimulated by 5'-monophosphate termini, to attack mRNAs from the 5'-end, causing their destabilization. The PNK-dependent pathway of degradation becomes effective 5 min postinfection, consistent with our finding that several minutes are required for PNK to accumulate after infection. Our work emphasizes the importance of the nature of the 5' terminus for mRNA stability and depicts a pathway of mRNA degradation with 5'- to 3'-polarity in cells devoid of 5'-3' exonucleases. It also ascribes a role for T4 PNK during normal phage development.     

Border Cave and the beginning of the Later Stone Age in South Africa

The transition from the Middle Stone Age (MSA) to the Later Stone Age (LSA) in South Africa was not associated with the appearance of anatomically modern humans and the extinction of Neandertals, as in the Middle to Upper Paleolithic transition in Western Europe. It has therefore attracted less attention, yet it provides insights into patterns of technological evolution not associated with a new hominin. Data from Border Cave (KwaZulu-Natal) show a strong pattern of technological change at approximately 44-42 ka cal BP, marked by adoption of techniques and materials that were present but scarcely used in the previous MSA, and some novelties. The agent of change was neither a revolution nor the advent of a new species of human. Although most evident in personal ornaments and symbolic markings, the change from one way of living to another was not restricted to aesthetics. Our analysis shows that: (i) at Border Cave two assemblages, dated to 45-49 and >49 ka, show a gradual abandonment of the technology and tool types of the post-Howiesons Poort period and can be considered transitional industries; (ii) the 44-42 ka cal BP assemblages are based on an expedient technology dominated by bipolar knapping, with microliths hafted with pitch from Podocarpus bark, worked suid tusks, ostrich eggshell beads, bone arrowheads, engraved bones, bored stones, and digging sticks; (iii) these assemblages mark the beginning of the LSA in South Africa; (iv) the LSA emerged by internal evolution; and (v) the process of change began sometime after 56 ka.