Differential Contributions of Dorso-Ventral and Rostro-Caudal Prefrontal White Matter Tracts to Cognitive Control in Healthy Older Adults

Prefrontal cortex mediates cognitive control by means of circuitry organized along dorso-ventral and rostro-caudal axes. Along the dorso-ventral axis, ventrolateral PFC controls semantic information, whereas dorsolateral PFC encodes task rules. Along the rostro-caudal axis, anterior prefrontal cortex encodes complex rules and relationships between stimuli, whereas posterior prefrontal cortex encodes simple relationships between stimuli and behavior. Evidence of these gradients of prefrontal cortex organization has been well documented in fMRI studies, but their functional correlates have not been examined with regard to integrity of underlying white matter tracts. We hypothesized that (a) the integrity of specific white matter tracts is related to cognitive functioning in a manner consistent with the dorso-ventral and rostro-caudal organization of the prefrontal cortex, and (b) this would be particularly evident in healthy older adults. We assessed three cognitive processes that recruit the prefrontal cortex and can distinguish white matter tracts along the dorso-ventral and rostro-caudal dimensions –episodic memory, working memory, and reasoning. Correlations between cognition and fractional anisotropy as well as fiber tractography revealed: (a) Episodic memory was related to ventral prefrontal cortex-thalamo-hippocampal fiber integrity; (b) Working memory was related to integrity of corpus callosum body fibers subserving dorsolateral prefrontal cortex; and (c) Reasoning was related to integrity of corpus callosum body fibers subserving rostral and caudal dorsolateral prefrontal cortex. These findings confirm the ventrolateral prefrontal cortex''s role in semantic control and the dorsolateral prefrontal cortex''s role in rule-based processing, in accordance with the dorso-ventral prefrontal cortex gradient. Reasoning-related rostral and caudal superior frontal white matter may facilitate different levels of task rule complexity. This study is the first to demonstrate dorso-ventral and rostro-caudal prefrontal cortex processing gradients in white matter integrity.     

Congenital Hypogonadotropic Hypogonadism during Childhood: Presentation and Genetic Analyses in 46 Boys

Background

The majority of the patients reported with mutations in isolated hypogonadotropic hypogonadism (HH) are adults. We analysed the presentation and the plasma inhibin B and anti-müllerian hormone (AMH) concentrations during childhood and adolescence, and compared them to the genetic results.

Methods

This was a retrospective, single-center study of 46 boys with HH.

Results

Fourteen (30.4%) had Kallmann syndrome (KS), 4 (8.7%) had CHARGE syndrome and 28 (60.9%) had HH without olfaction deficit nor olfactive bulb hypoplasia. Eighteen (39%) had an associated malformation or syndromes. At diagnosis, 22 (47.8%) boys were aged <one year, 9 (19%) 1–11 and 15 (32.6%) 11–17.6 years. They presented with micropenis (n = 32, 69.6%, including all those <one year), cryptorchidism (n = 32, 69.6%, unilateral in 8, bilateral in 24), and/or pubertal delay (n = 11). The plasma inhibin B concentrations were normal in 8 (3 KS including one CHARGE and 5 other HH), at the lower limit of the normal in 6 and decreased in 13 (48%) boys. The AMH concentrations were normal in 15 (6 KS including one CHARGE and 9 other HH) and decreased in 12 (44%) boys. In addition to the CHD7 gene mutations in 4 patients with CHARGE, mutations were found in 5/26 other boys analysed including one in KAL1 gene with STS, 2 in FGFR1 gene, one in PROKR2 gene and one in GnRHR gene.

Conclusions

The presence of micropenis in neonate, particularly if associated with cryptorchidism, is an indication to look for gonadotropin deficiency isolated or associated with other hypothalamic-pituitary deficiencies. Inhibin B and AMH concentrations are suggestive if low, but they may be normal. Despite the high frequency of the associated malformations and excluding the patients with CHARGE or ichtyosis, the 4 patients with mutations had no family history or malformation. This suggests that many other genes are involved.     

How can we live with ourselves? Universities and the attempt to reconcile learning and doing

This article revisits recent debates about the responsibilities of public scholarship. The piece argues that writing in a range of fields has engaged with issues of racism, in particular as racism has been manifested in the ‘war on terror’, but that this discussion has been muted within the sub-field of race and ethnic studies. There is a discussion of the impact of pressures to demonstrate the ‘usefulness’ of research to a wider public and the limits that this can place on the formulation of research. This argument is expanded through consideration of the author's experience of researching and lobbying with community and campaigning groups. The piece goes on to consider the implications of the marketization of higher education for critical scholarship and concludes that there is value in a more ‘private’ sociology that may not be easily accommodated in the marketized university.     

Cloning, characterization and expression of a chloroplastic fructose-1,6-bisphosphatase from Porteresia coarctata conferring salt-tolerance in transgenic tobacco

A gene coding for the chloroplastic fructose 1,6-bisphosphatase (PcCFR) in Porteresia coarctata Tateoka (Roxb.), a halophytic wild rice, has been isolated along with its rice (Oryza sativa; var. indica) homologue (OsCFR), cloned and sequenced. Comparison between the nucleotide and deduced amino acid sequences of these two revealed a difference in five amino acid residues, namely Glu¹⁴, Thr²⁴, Ala⁴⁸, Ala¹⁶³ and Arg²⁹⁶ in OsCFR which have been found to be replaced by Ser¹⁴, Ile²⁴, Ser⁴⁸, Ser¹⁶³ and Lys²⁹⁶ in PcCFR respectively. The purified recombinant PcCFR is found to retain its enzymatic activity in presence of up to 500 mM NaCl in vitro as opposed to OsCFR, which is inactivated even at lower salt concentration. The six in vitro point mutant proteins of PcCFR showed varied degree of sensitivity towards high salt, with the maximum OsCFR-like effect in the triple mutant S¹⁴A-S⁴⁸A-S¹⁶³A suggesting a possible concerted role of all three serine residues in the in vitro salt tolerance property of PcCFR protein. Transgenic tobacco plants with chloroplast targeted PcCFR and OsCFR gene(s) have been developed under constitutive expression of CaMV 35S promoter and NOS terminator. The PcCFR transgenics showed better plant growth during exposure to salt stress in comparison to either the OsCFR or the empty vector transformed plants. The PcCFR transgenics also revealed enhanced photosynthetic efficiency coupled with protection to both photodamage of PSII and chlorophyll degradation through better reactive oxygen species scavenging at higher concentration of NaCl during late salt-stress growth.     

Diosgenin improves vascular function by increasing aortic eNOS expression, normalize dyslipidemia and ACE activity in chronic renal failure rats

In recent years, the role of endothelial dysfunction (ED) and excessive oxidative stress in the development of cardiovascular diseases has been highlighted. The aim of the present study is to evaluate the effect of diosgenin, an antioxidant on chronic renal failure (CRF) induced vascular dysfunction. CRF was induced by feeding the rats with a diet containing 0.75 % adenine and diosgenin was given orally (everyday at the dose of 40 mg/kg). Isometric force measurement was performed on isolated aortic rings in organ baths. Levels of reduced glutathione (GSH), nitric oxide metabolites, and endothelial nitric oxide synthase mRNA in rat aorta were examined. Further, plasma lipid profile, activity of enzymes of lipid metabolism, and aortic angiotensin converting enzyme (ACE) also studied. The overall results have proved that diosgenin attenuates CRF-induced impairment in acetylcholine induced endothelium-dependent and sodium nitroprusside induced endothelium-independent vascular relaxation. Moreover, it elevates the GSH and restores the eNOS mRNA expression level. CRF-induced dyslipidemia and ACE activity was also inhibited by diosgenin treatment. This study indicates that diosgenin have enough potential to protect vasculature against oxidative stress, dyslipidemia which in turn improves the vascular function in CRF milieu.     

Rejoining of cut wounds by engineered gelatin–keratin glue

Background

Rejoining of cut tissue ends of a critical site challenges clinicians. The toxicity, antigenicity, low adhesive strength, flexibility, swelling and cost of the currently employed glue demands an alternative. Engineered gelatin–keratin glue (EGK-glue) described in the present study was found to be suitable for wet tissue approximation.

Methods

EGK-glue was prepared by engineering gelatin with caffeic acid using EDC and conjugating with keratin by periodate oxidation. UV–visible, ¹H NMR and circular dichroism analyses followed by experiments on gelation time, rheology, gel adhesive strength (in vitro), wet tissue approximation (in vivo), H&E staining of tissue sections at scheduled time intervals and tensile strength of the healed skin were carried out to assess the effectiveness of the EGK-glue in comparison with fibrin glue and cyanoacrylate.

Results

Results of UV–visible, NMR and CD analyses confirmed the functionalization and secondary structural changes. Increasing concentration of keratin reduces the gelation time (< 15 s). Lap-shear test demonstrates the maximum adhesive strength of 16.6 ± 1.2 kPa. Results of hemocompatibility and cytocompatibility studies suggested the suitability of the glue for clinical applications. Tissue approximation property assessed using the incision wound model (Wistar strain) in comparison with cyanoacrylate and fibrin glue suggested, that EGK-glue explicitly accelerates the rejoining of tissue with a 1.86 fold increase in skin tensile strength after healing.

Conclusions

Imparting quinone moiety to gelatin–keratin conjugates through caffeic acid and a weaker oxidizing agent provides an adhesive glue with appreciable strength, and hemocompatible, cytocompatible and biodegradable properties, which, rejoin the cut tissue ends effectively.

General significance

EGK-glue obtained in the present study finds wide biomedical/clinical applications.     

Symbiotic influence of endophytic Bacillus pumilus on growth promotion and probiotic potential of the medicinal plant Ocimum sanctum

Bacillus pumilus was isolated from surface-sterilized tissues of the medicinal plant Ocimum sanctum. Scanning electron microscopic (SEM) imaging confirmed the presence of a rod shaped bacterium within the plant tissues. The bacterium was identified as B. pumilus by biochemical analyses and 16S rRNA gene sequencing. In vitro analyses indicate that the isolated strain of B. pumilus was endowed with multiple plant growth promotion (PGP) traits such as phosphate solubilization and the production of indole acetic acid (IAA), siderophore and hydrogen cyanide (HCN). Phosphate solubilization (37.3 μg ml^?1) and IAA production (36.7 μg ml^?1) by the isolate was found to reach a maximum after 60 h of incubation. Siderophore mediated iron sequestration by B. pumilus may confer a competitive advantage to the host with respect to pathogen inhibition. Siderophore produced by the isolate was found to be of a trihydroxamate type with hexadentate nature. The B. pumilus isolate also exhibited cellulolytic, proteolytic and chitinolytic activity. Cell free supernatant, culture filtrates of the isolate were found to suppress the growth of fungal phytopathogens. The culture filtrate retained its antifungal activity even after exposure to heat. In addition to PGP, the isolate exhibited probiotic properties such as acid tolerance (pH2), bile salt tolerance (2 %), auto-aggregation, antibiotic resistance and the absence of haemolytic activity. These finding suggest the possibility of utilizing this endophytic strain of B. pumilus as a bioinoculant to enhance plant growth and also as a probiotic.     

Effects of Pentoxifylline on Liver and Thymus of Plasmodium berghei ANKA Infected Swiss Albino Mice

Infection of Swiss albino mice with Plasmodium berghei ANKA (PbA), a lethal strain, led to injury of the liver, thymic atrophy and high host mortality. Action of pentoxifylline (PTX), an inhibitor of TNF-α (tumor necrosis factor alpha), was investigated on hepatic necrosis, thymic atrophy, increased percentage of Sub G0/G1 hepatic and thymic populations, parasitemia and survivability of the infected mice host. Our data suggest the importance of PTX in mice survival and curing of liver cirrhosis, without affecting the parasitemic condition of the infected mice. Histomorphological changes were well evident from the appearance of hypertrophied hepatic cells with abundance of pigments. In the thymus no cortico-medullary demarcation was observed with presence of hypertrophied thymocytes. Hyperplasia of hepatic cells in the Sub-G0/G1 stage as revealed by flow cytometric analyses, was suppressed by PTX which is an indication of apoptotic effect of PTX in mice. Mice treated with PTX showed a significant decrease of necrotic areas in liver and thymus, suggesting that PTX treatment controls TNF-α effect, and thus PTX may be used as an adjuvant in the treatment of malaria.     

Start Codon Targeted (SCoT) marker reveals genetic diversity of Dendrobium nobile Lindl., an endangered medicinal orchid species

Genetic variability in the wild genotypes of Dendrobium nobile Lindl. collected from different parts of Northeast India, was analyzed using a Start Codon Targeted (SCoT) marker system. A total of sixty individuals comprising of six natural populations were investigated for the existing natural genetic diversity. One hundred and thirty two (132) amplicons were produced by SCoT marker generating 96.21% polymorphism. The PIC value of the SCoT marker system was 0.78 and the Rp values of the primers ranged between 4.43 and 7.50. The percentage of polymorphic loci (Pp) ranging from 25% to 56.82%, Nei's gene diversity (h) from 0.08 to 0.15 with mean Nei's gene diversity of 0.28, and Shannon's information index (I) values ranging from 0.13 to 0.24 with an average value of 0.43 were recorded. The gene flow value (0.37) and the diversity among populations (0.57) demonstrated higher genetic variation among the populations. Analysis of molecular variance (AMOVA) showed 43.37% of variation within the populations, whereas 56.63% variation was recorded among the populations. Cluster analysis also reveals high genetic variation among the genotypes. Present investigation suggests the effectiveness of SCoT marker system to estimate the genetic diversity of D. nobile and that it can be seen as a preliminary point for future research on the population and evolutionary genetics of this endangered orchid species of medicinal importance.