Unraveling the Ultrafast Photochemical Dynamics of Nitrobenzene in Aqueous Solution.

Nitroaromatic compounds are major constituents of the brown carbon aerosol particles in the troposphere that absorb near-ultraviolet (UV) and visible solar radiation and have a profound effect on the Earth's climate. The primary sources of brown carbon include biomass burning, forest fires, and residential burning of biofuels, and an important secondary source is photochemistry in aqueous cloud and fog droplets. Nitrobenzene is the smallest nitroaromatic molecule and a model for the photochemical behavior of larger nitroaromatic compounds. Despite the obvious importance of its droplet photochemistry to the atmospheric environment, there have not been any detailed studies of the ultrafast photochemical dynamics of nitrobenzene in aqueous solution. Here, we combine femtosecond transient absorption spectroscopy, time-resolved infrared spectroscopy, and quantum chemistry calculations to investigate the primary steps following the near-UV (λ ≥ 340 nm) photoexcitation of aqueous nitrobenzene. To understand the role of the surrounding water molecules in the photochemical dynamics of nitrobenzene, we compare the results of these investigations with analogous measurements in solutions of methanol, acetonitrile, and cyclohexane. We find that vibrational energy transfer to the aqueous environment quenches internal excitation, and therefore, unlike the gas phase, we do not observe any evidence for formation of photoproducts on timescales up to 500 ns. We also find that hydrogen bonding between nitrobenzene and surrounding water molecules slows the S1/S0 internal conversion process.

Automated protocols for delineating human hippocampal subfields from 3 Tesla and 7 Tesla magnetic resonance imaging data.

Researchers who study the human hippocampus are naturally interested in how its subfields function. However, many researchers are precluded from examining subfields because their manual delineation from magnetic resonance imaging (MRI) scans (still the gold standard approach) is time consuming and requires significant expertise. To help ameliorate this issue, we present here two protocols, one for 3T MRI and the other for 7T MRI, that permit automated hippocampus segmentation into six subregions, namely dentate gyrus/cornu ammonis (CA)4, CA2/3, CA1, subiculum, pre/parasubiculum, and uncus along the entire length of the hippocampus. These protocols are particularly notable relative to existing resources in that they were trained and tested using large numbers of healthy young adults (n = 140 at 3T, n = 40 at 7T) whose hippocampi were manually segmented by experts from MRI scans. Using inter-rater reliability analyses, we showed that the quality of automated segmentations produced by these protocols was high and comparable to expert manual segmenters. We provide full open access to the automated protocols, and anticipate they will save hippocampus researchers a significant amount of time. They could also help to catalyze subfield research, which is essential for gaining a full understanding of how the hippocampus functions.

Ophthalmic and Neuroimaging Associations In Optic Nerve Hypoplasia/Septo-Optic-Pituitary Dysplasia.

BACKGROUND: Optic nerve hypoplasia (ONH) and septo-optic-pituitary dysplasia (SOD) are neurodevelopmental disorders associated with congenital visual impairment. Our aim was to investigate associations between several ophthalmic and neuroimaging features in patients with ONH/SOD. METHODS: A retrospective chart and neuroimaging review was performed in patients with ONH/SOD. Ophthalmic signs (e.g., monocular best-corrected visual acuity [BCVA], nystagmus, and strabismus) and neuroimaging data were extracted and their associations were investigated. RESULTS: There were 128 patients (70 males) with ONH/SOD who had neuroimaging. Their mean age at the end of the study was 13.2 (SD: 7.5) years. Ophthalmic data were available on 102 patients (58 males). BCVA varied from normal to no light perception. There were statistically significant associations between: (A) Reduced optic nerve or chiasm size on neuroimaging and more severely impaired BCVA and (B) laterality of the reduced optic nerve or chiasm size on neuroimaging and laterality of: (1) The eye with reduced BCVA, (2) small optic disc size, and (3) RAPD, if present (p ≤ 0.0002 each). The presence of symmetrically small optic nerves on MRI was significantly more common in patients with nystagmus than when nystagmus was absent (N = 96, 75% vs. 38.6%, p < 0.0001). The presence of neuronal migration disorders, their type and laterality were not associated with BCVA and laterality of the reduced BCVA. CONCLUSION: The functional and structural associations in ONH are consistent with the impaired visual function that results from the hypoplastic anterior visual pathways. However, these associations were not perfectly concordant making prediction of adult BCVA challenging in these patients.

Good Vibrations Report on the DNA Quadruplex Binding of an Excited State Amplified Ruthenium Polypyridyl IR Probe.

The nitrile containing Ru(II)polypyridyl complex [Ru(phen)2(11,12-dCN-dppz)]2+ (1) is shown to act as a sensitive infrared probe of G-quadruplex (G4) structures. UV-visible absorption spectroscopy reveals enantiomer sensitive binding for the hybrid htel(K) and antiparallel htel(Na) G4s formed by the human telomer sequence d[AG3(TTAG3)3]. Time-resolved infrared (TRIR) of 1 upon 400 nm excitation indicates dominant interactions with the guanine bases in the case of Λ-1/htel(K), Δ-1/htel(K), and Λ-1/htel(Na) binding, whereas Δ-1/htel(Na) binding is associated with interactions with thymine and adenine bases in the loop. The intense nitrile transient at 2232 cm-1 undergoes a linear shift to lower frequency as the solution hydrogen bonding environment decreases in DMSO/water mixtures. This shift is used as a sensitive reporter of the nitrile environment within the binding pocket. The lifetime of 1 in D2O (ca. 100 ps) is found to increase upon DNA binding, and monitoring of the nitrile and ligand transients as well as the diagnostic DNA bleach bands shows that this increase is related to greater protection from the solvent environment. Molecular dynamics simulations together with binding energy calculations identify the most favorable binding site for each system, which are in excellent agreement with the observed TRIR solution study. This study shows the power of combining the environmental sensitivity of an infrared (IR) probe in its excited state with the TRIR DNA "site effect" to gain important information about the binding site of photoactive agents and points to the potential of such amplified IR probes as sensitive reporters of biological environments.

Coumarin C-H Functionalization by Mn(I) Carbonyls: Mechanistic Insight by Ultra-Fast IR Spectroscopic Analysis.

Mn(I) C-H functionalization of coumarins provides a versatile and practical method for the rapid assembly of fused polycyclic pyridinium-containing coumarins in a regioselective manner. The synthetic strategy enables application of bench-stable organomanganese reagents in both photochemical- and thermal-promoted reactions. The cyclomanganated intermediates, and global reaction system, provide an ideal testing ground for structural characterization of the active Mn(I) carbonyl-containing species, including transient species observable by ultra-fast time-resolved spectroscopic methods. The thermodynamic reductive elimination product, solely encountered from reaction between alkynes and air-stable organometallic cyclomanganated coumarins, has enabled characterization of a critical seven-membered Mn(I) intermediate, detected by time-resolved infrared spectroscopy, enabling the elucidation of the temporal profile of key steps in the reductive elimination pathway. Quantitative data are provided. Manganated polycyclic products are readily decomplexed by AgBF4 , opening-up an efficient route to the formation of π-extended hybrid coumarin-pyridinium compounds.

Microbial Catabolic Activity: Methods, Pertinence, and Potential Interest for Improving Microbial Inoculant Efficiency.

Microbial catabolic activity (MCA) defined as the degrading activity of microorganisms toward various organic compounds for their growth and energy is commonly used to assess soil microbial function potential. For its measure, several methods are available including multi-substrate-induced respiration (MSIR) measurement which allow to estimate functional diversity using selected carbon substrates targeting specific biochemical pathways. In this review, the techniques used to measure soil MCA are described and compared with respect to their accuracy and practical use. Particularly the efficiency of MSIR-based approaches as soil microbial function indicators was discussed by (i) showing their sensitivity to different agricultural practices including tillage, amendments, and cropping systems and (ii) by investigating their relationship with soil enzyme activities and some soil chemical properties (pH, soil organic carbon, cation exchange capacity). We highlighted the potential of these MSIR-based MCA measurements to improve microbial inoculant composition and to determine their potential effects on soil microbial functions. Finally, we have proposed ideas for improving MCA measurement notably through the use of molecular tools and stable isotope probing which can be combined with classic MSIR methods. Graphical abstract describing the interrelation between the different parts and the concepts developed in the review.

A new Rothamsted long-term field experiment for the twenty-first century: principles and practice.

Agriculture faces potentially competing societal demands to produce food, fiber and fuel while reducing negative environmental impacts and delivering regulating, supporting and cultural ecosystem services. This necessitates a new generation of long-term agricultural field experiments designed to study the behavior of contrasting cropping systems in terms of multiple outcomes. We document the principles and practices of a new long-term experiment of this type at Rothamsted, established at two contrasting sites in 2017 and 2018, and report initial yield data at the crop and system level. The objective of the Large-Scale Rotation Experiment was to establish gradients of system properties and outcomes to improve our fundamental understanding of UK cropping systems. It is composed of four management factors-phased rotations, cultivation (conventional vs reduced tillage), nutrition (additional organic amendment vs standard mineral fertilization) and crop protection (conventional vs smart crop protection). These factors were combined in a balanced design resulting in 24 emergent cropping systems at each site and can be analyzed at the level of the system or component management factors. We observed interactions between management factors and with the environment on crop yields, justifying the systems level, multi-site approach. Reduced tillage resulted in lower wheat yields but the effect varied with rotation, previous-crop and site. Organic amendments significantly increased spring barley yield by 8% on average though the effect again varied with site. The plowed cropping systems tended to produce higher caloric yield overall than systems under reduced tillage. Additional response variables are being monitored to study synergies and trade-offs with outcomes other than yield at the cropping system level. The experiment has been established as a long-term resource for inter-disciplinary research. By documenting the design process, we aim to facilitate the adoption of similar approaches to system-scale agricultural experimentation to inform the transition to more sustainable cropping systems. Supplementary Information: The online version contains supplementary material available at 10.1007/s13593-023-00914-8.

Bowel Histology of CVID Patients Reveals Distinct Patterns of Mucosal Inflammation.

Diarrhea is the commonest gastrointestinal symptom in patients with common variable immunodeficiency (CVID). Different pathologies in patients' bowel biopsies have been described and links with infections have been demonstrated. The aim of this study was to analyze the bowel histology of CVID patients in the Royal-Free-Hospital (RFH) London CVID cohort. Ninety-five bowel histology samples from 44 adult CVID patients were reviewed and grouped by histological patterns. Reasons for endoscopy and possible causative infections were recorded. Lymphocyte phenotyping results were compared between patients with different histological features. There was no distinctive feature that occurred in most diarrhea patients. Out of 44 patients (95 biopsies), 38 lacked plasma cells. In 14 of 21 patients with nodular lymphoid hyperplasia (NLH), this was the only visible pathology. In two patients, an infection with Giardia lamblia was associated with NLH. An IBD-like picture was seen in two patients. A coeliac-like picture was found in six patients, four of these had norovirus. NLH as well as inflammation often occurred as single features. There was no difference in blood lymphocyte phenotyping results comparing groups of histological features. We suggest that bowel histology in CVID patients with abdominal symptoms falls into three major histological patterns: (i) a coeliac-like histology, (ii) IBD-like changes, and (iii) NLH. Most patients, but remarkably not all, lacked plasma cells. CVID patients with diarrhea may have an altered bowel histology due to poorly understood and likely diverse immune-mediated mechanisms, occasionally driven by infections.

microRNA-seq of cartilage reveals an overabundance of miR-140-3p which contains functional isomiRs.

miR-140 is selectively expressed in cartilage. Deletion of the entire Mir140 locus in mice results in growth retardation and early-onset osteoarthritis-like pathology; however, the relative contribution of miR-140-5p or miR-140-3p to the phenotype remains to be determined. An unbiased small RNA sequencing approach identified miR-140-3p as significantly more abundant (>10-fold) than miR-140-5p in human cartilage. Analysis of these data identified multiple miR-140-3p isomiRs differing from the miRBase annotation at both the 5' and 3' end, with >99% having one of two seed sequences (5' bases 2-8). Canonical (miR-140-3p.2) and shifted (miR-140-3p.1) seed isomiRs were overexpressed in chondrocytes and transcriptomics performed to identify targets. miR-140-3p.1 and miR-140-3p.2 significantly down-regulated 694 and 238 genes, respectively, of which only 162 genes were commonly down-regulated. IsomiR targets were validated using 3'UTR luciferase assays. miR-140-3p.1 targets were enriched within up-regulated genes in rib chondrocytes of Mir140-null mice and within down-regulated genes during human chondrogenesis. Finally, through imputing the expression of miR-140 from the expression of the host gene WWP2 in 124 previously published data sets, an inverse correlation with miR-140-3p.1 predicted targets was identified. Together these data suggest the novel seed containing isomiR miR-140-3p.1 is more functional than original consensus miR-140-3p seed containing isomiR.

Background to new treatments for COVID-19, including its chronicity, through altering elements of the cytokine storm.

Anti-tumour necrosis factor (TNF) biologicals, Dexamethasone and rIL-7 are of considerable interest in treating COVID-19 patients who are in danger of, or have become, seriously ill. Yet reducing sepsis mortality by lowering circulating levels of TNF lost favour when positive endpoints in earlier simplistic models could not be reproduced in well-conducted human trials. Newer information with anti-TNF biologicals has encouraged reintroducing this concept for treating COVID-19. Viral models have had encouraging outcomes, as have the effects of anti-TNF biologicals on community-acquired COVID-19 during their long-term use to treat chronic inflammatory states. The positive outcome of a large scale trial of dexamethasone, and its higher potency late in the disease, harmonises well with its capacity to enhance levels of IL-7Rα, the receptor for IL-7, a cytokine that enhances lymphocyte development and is increased during the cytokine storm. Lymphoid germinal centres required for antibody-based immunity can be harmed by TNF, and restored by reducing TNF. Thus the IL-7- enhancing activity of dexamethasone may explain its higher potency when lymphocytes are depleted later in the infection, while employing anti-TNF, for several reasons, is much more logical earlier in the infection. This implies dexamethasone could prove to be synergistic with rIL-7, currently being trialed as a COVID-19 therapeutic. The principles behind these COVID-19 therapies are consistent with the observed chronic hypoxia through reduced mitochondrial function, and also the increased severity of this disease in ApoE4-positive individuals. Many of the debilitating persistent aspects of this disease are predictably susceptible to treatment with perispinal etanercept, since they have cerebral origins.

MicroRNA-Based Diagnosis and Therapy.

MicroRNAs (miRNAs) are a group of endogenous non-coding RNAs that regulate gene expression. Alteration in miRNA expression results in changes in the profile of genes involving a range of biological processes, contributing to numerous human disorders. With high stability in human fluids, miRNAs in the circulation are considered as promising biomarkers for diagnosis, as well as prognosis of disease. In addition, the translation of miRNA-based therapy from a research setting to clinical application has huge potential. The aim of the current review is to: (i) discuss how miRNAs traffic intracellularly and extracellularly; (ii) emphasize the role of circulating miRNAs as attractive potential biomarkers for diagnosis and prognosis; (iii) describe how circulating microRNA can be measured, emphasizing technical problems that may influence their relative levels; (iv) highlight some of the circulating miRNA panels available for clinical use; (v) discuss how miRNAs could be utilized as novel therapeutics, and finally (v) update those miRNA-based therapeutics clinical trials that could potentially lead to a breakthrough in the treatment of different human pathologies.

The microRNA-455 Null Mouse Has Memory Deficit and Increased Anxiety, Targeting Key Genes Involved in Alzheimer's Disease.

The complete molecular mechanisms underlying the pathophysiology of Alzheimer's disease (AD) remain to be elucidated. Recently, microRNA-455-3p has been identified as a circulating biomarker of early AD, with increased expression in post-mortem brain tissue of AD patients. MicroRNA-455-3p also directly targets and down-regulates APP, with the overexpression of miR-455-3p suppressing its toxic effects. Here, we show that miR-455-3p expression decreases with age in the brains of wild-type mice. We generated a miR-455 null mouse utilising CRISPR-Cas9 to explore its function further. Loss of miR-455 resulted in increased weight gain, potentially indicative of metabolic disturbances. Furthermore, performance on the novel object recognition task diminished significantly in miR-455 null mice (p = 0.004), indicating deficits in recognition memory. A slight increase in anxiety was also captured on the open field test. BACE1 and TAU were identified as new direct targets for miR-455-3p, with overexpression of miR-455-3p leading to a reduction in the expression of APP, BACE1 and TAU in neuroblastoma cells. In the hippocampus of miR-455 null mice at 14 months of age, the levels of protein for APP, BACE1 and TAU were all increased. Such findings reinforce the involvement of miR-455 in AD progression and demonstrate its action on cognitive performance.

Selected Ophthalmological Features in Children with Septo-Optic Dysplasia and Optic Nerve Hypoplasia.

Septo-optic dysplasia (SOD) and optic nerve hypoplasia (ONH) cause congenital visual impairment. Their aetiology is mostly unknown. Our aim was to investigate the prevalence of selected ophthalmological features in patients with these disorders. A chart review was performed on patients with SOD/ONH. Ophthalmological data were extracted. There were 102 patients (56 males). The median age at the end of the study was 12.7 years. Best-corrected visual acuity ranged from normal to no light perception. Bilateral ONH was more common than unilateral ONH. Strabismus (85%) and to a lesser extent nystagmus (52%) were both very common in our cohort. Patients with esotropia had worse visual acuity than those who had exotropia. The presence of nystagmus was more likely in cases with bilateral ONH. Therefore, patients with SOD/ONH may have normal visual acuity. Many have strabismus, which may cause amblyopia thereby further decreasing visual acuity. Nystagmus occurs commonly and its presence typically indicates bilateral ONH.

Direct Observation of Reactive Intermediates by Time-Resolved Spectroscopy Unravels the Mechanism of a Radical-Induced 1,2-Metalate Rearrangement.

Radical-induced 1,2-metalate rearrangements of boronate complexes are an emerging and promising class of reactions that allow multiple new bonds to be formed in a single, tunable reaction step. These reactions involve the addition of an alkyl radical, typically generated from an alkyl iodide under photochemical activation, to a boronate complex to produce an α-boryl radical intermediate. From this α-boryl radical, there are two plausible reaction pathways that can trigger the product forming 1,2-metalate rearrangement: iodine atom transfer (IAT) or single electron transfer (SET). Previous steady-state techniques have struggled to differentiate these pathways. Here we apply state-of-the-art time-resolved infrared absorption spectroscopy to resolve all the steps in the reaction cycle by mapping production and consumption of the reactive intermediates over picosecond to millisecond time scales. We apply this technique to a recently reported reaction involving the addition of an electron-deficient alkyl radical to the strained σ-bond of a bicyclo[1.1.0]butyl boronate complex to form a cyclobutyl boronic ester. We show that the previously proposed SET mechanism does not adequately account for the observed spectral and kinetic data. Instead, we demonstrate that IAT is the preferred pathway for this reaction and is likely to be operative for other reactions of this type.

Singlet and Triplet Contributions to the Excited-State Activities of Dihydrophenazine, Phenoxazine, and Phenothiazine Organocatalysts Used in Atom Transfer Radical Polymerization.

The photochemical dynamics of three classes of organic photoredox catalysts employed in organocatalyzed atom-transfer radical polymerization (O-ATRP) are studied using time-resolved optical transient absorption and fluorescence spectroscopy. The nine catalysts selected for study are examples of N-aryl and core-substituted dihydrophenazine, phenoxazine and phenothiazine compounds with varying propensities for control of polymerization outcomes. Excited singlet-state lifetimes extracted from the spectroscopic measurements are reported in N,N-dimethylformamide (DMF), dichloromethane (DCM), and toluene. Ultrafast (<200 fs to 3 ps) electronic relaxation of the photocatalysts after photoexcitation at near-UV wavelengths (318-390 nm) populates the first singlet excited state (S1). The S1-state lifetimes range from 130 ps to 40 ns with a considerable dependence on the photocatalyst structure and the solvent. The competition between ground electronic state recovery and intersystem crossing controls triplet state populations and is a minor pathway in the dihydrophenazine derivatives but is of greater importance for phenoxazine and phenothiazine catalysts. A comparison of our results with previously reported O-ATRP performances of the various photoredox catalysts shows that high triplet-state quantum yields are not a prerequisite for controlling polymer dispersity. For example, the photocatalyst 5,10-bis(4-cyanophenyl)-5,10-dihydrophenazine, shown previously to exert good polymerization control, possesses the shortest S1-state lifetime (135 ps in DMF and 180 ps in N,N-dimethylacetamide) among the nine examples reported here and a negligible triplet-state quantum yield. The results call for a re-evaluation of the excited-state properties of most significance in governing the photocatalytic behavior of organic photoredox catalysts in O-ATRP reactions.

Direct Observation of the Microscopic Reverse of the Ubiquitous Concerted Metalation Deprotonation Step in C-H Bond Activation Catalysis.

The ability of carboxylate groups to promote the direct functionalization of C-H bonds in organic compounds is unquestionably one of the most important discoveries in modern chemical synthesis. Extensive computational studies have indicated that this process proceeds through the deprotonation of a metal-coordinated C-H bond by the basic carboxylate, yet experimental validation of these predicted mechanistic pathways is limited and fraught with difficulty, mainly as rapid proton transfer is frequently obscured in ensemble measures in multistep reactions (i.e., a catalytic cycle consisting of several steps). In this paper, we describe a strategy to experimentally observe the microscopic reverse of the key C-H bond activation step underpinning functionalization processes (viz. M-C bond protonation). This has been achieved by utilizing photochemical activation of the thermally robust precursor [Mn(ppy)(CO)4] (ppy = metalated 2-phenylpyridine) in neat acetic acid. Time-resolved infrared spectroscopy on the picosecond-millisecond time scale allows direct observation of the states involved in the proton transfer from the acetic acid to the cyclometalated ligand, providing direct experimental evidence for the computationally predicted reaction pathways. The power of this approach to probe the mechanistic pathways in transition-metal-catalyzed reactions is demonstrated through experiments performed in toluene solution in the presence of PhC2H and HOAc. These allowed for the observation of sequential displacement of the metal-bound solvent by the alkyne, C-C bond formation though insertion in the Mn-C bond, and a slower protonation step by HOAc to generate the product of a Mn(I)-catalyzed C-H bond functionalization reaction.

Adenine Radical Cation Formation by a Ligand-Centered Excited State of an Intercalated Chromium Polypyridyl Complex Leads to Enhanced DNA Photo-oxidation.

Assessment of the DNA photo-oxidation and synthetic photocatalytic activity of chromium polypyridyl complexes is dominated by consideration of their long-lived metal-centered excited states. Here we report the participation of the excited states of [Cr(TMP)2dppz]3+ (1) (TMP = 3,4,7,8-tetramethyl-1,10-phenanthroline; dppz = dipyrido[3,2-a:2',3'-c]phenazine) in DNA photoreactions. The interactions of enantiomers of 1 with natural DNA or with oligodeoxynucleotides with varying AT content (0-100%) have been studied by steady state UV/visible absorption and luminescence spectroscopic methods, and the emission of 1 is found to be quenched in all systems. The time-resolved infrared (TRIR) and visible absorption spectra (TA) of 1 following excitation in the region between 350 to 400 nm reveal the presence of relatively long-lived dppz-centered states which eventually yield the emissive metal-centered state. The dppz-localized states are fully quenched when bound by GC base pairs and partially so in the presence of an AT base-pair system to generate purine radical cations. The sensitized formation of the adenine radical cation species (A•+T) is identified by assigning the TRIR spectra with help of DFT calculations. In natural DNA and oligodeoxynucleotides containing a mixture of AT and GC of base pairs, the observed time-resolved spectra are consistent with eventual photo-oxidation occurring predominantly at guanine through hole migration between base pairs. The combined targeting of purines leads to enhanced photo-oxidation of guanine. These results show that DNA photo-oxidation by the intercalated 1, which locates the dppz in contact with the target purines, is dominated by the LC centered excited state. This work has implications for future phototherapeutics and photocatalysis.

The relationship between hippocampal subfield volumes and autobiographical memory persistence.

Structural integrity of the human hippocampus is widely acknowledged to be necessary for the successful encoding and retrieval of autobiographical memories. However, evidence for an association between hippocampal volume and the ability to recall such memories in healthy individuals is mixed. Here we examined this issue further by combining two approaches. First, we focused on the anatomically distinct subregions of the hippocampus where more nuanced associations may be expressed compared to considering the whole hippocampal volume. A manual segmentation protocol of hippocampal subregions allowed us to separately calculate the volumes of the dentate gyrus/CA4, CA3/2, CA1, subiculum, pre/parasubiculum and uncus. Second, a critical feature of autobiographical memories is that they can span long time periods, and so we sought to consider how memory details persist over time by conducting a longitudinal study whereby participants had to recall the same autobiographical memories on two visits spaced 8 months apart. Overall, we found that there was no difference in the total number of internal (episodic) details produced at Visits 1 and 2. However, further probing of detail subcategories revealed that specifically the amount of subjective thoughts and emotions included during recall had declined significantly by the second visit. We also observed a strong correlation between left pre/parasubiculum volume and the amount of autobiographical memory internal details produced over time. This positive relationship was evident for particular facets of the memories, with remembered events, perceptual observations and thoughts and emotions benefitting from greater volume of the left pre/parasubiculum. These preliminary findings expand upon existing functional neuroimaging evidence by highlighting a potential link between left pre/parasubiculum volume and autobiographical memory. A larger pre/parasubiculum appears not only to protect against memory decay, but may possibly enhance memory persistence, inviting further scrutiny of the role of this brain region in remote autobiographical memory retrieval.

Light- and Manganese-Initiated Borylation of Aryl Diazonium Salts: Mechanistic Insight on the Ultrafast Time-Scale Revealed by Time-Resolved Spectroscopic Analysis.

Manganese-mediated borylation of aryl/heteroaryl diazonium salts emerges as a general and versatile synthetic methodology for the synthesis of the corresponding boronate esters. The reaction proved an ideal testing ground for delineating the Mn species responsible for the photochemical reaction processes, that is, involving either Mn radical or Mn cationic species, which is dependent on the presence of a suitably strong oxidant. Our findings are important for a plethora of processes employing Mn-containing carbonyl species as initiators and/or catalysts, which have considerable potential in synthetic applications.

The Differential Diagnosis of Intrahepatic Ductular Reaction in Medical Liver Biopsy.

Intrahepatic ductular reaction is a pathologic proliferation of phenotypical biliary channels. Ductular reactions aim to restore compromised physiological function after liver injury and are one of the archetypal responses of the liver to a wide variety of etiologies, among them are parenchymal loss, biliary tract disease, neoplasms, after liver transplantation, and several pediatric liver diseases. The types and extent of ductular reactions can vary, according to the etiological insult. In this review, the authors will first consider the different mechanisms for ductular reactions and their relevance for liver regeneration. After, the authors will discuss our approach to differential diagnosis for ductular reactions in different patient groups, taking into account clinical history and potential pitfalls. The authors provide an algorithmic approach for practicing pathologists and trainees when confronted by a ductular reaction in a liver biopsy.