The contribution of the cerebellum to mental and social functions in developmental age

Here we present the data concerning the intellectual, language, and frontal performances of 24 children who have undergone surgery because of cerebellar hemisphere or vermis tumors and one girl with viral cerebellitis. The children with right cerebellar tumors presented auditory sequential memory and language processing disturbances; those with left cerebellar tumors showed deficits in spatial tests and visual sequential memory. The girl with cerebellitis showed a complex neuropsychological picture with impairment in processing language and general sequential functions. Lesions of the vermis lead to two pictures: (1) a postsurgical mutism that could be subdivided into speech disorders (even to the extent of anarthria) and true language disturbances similar to frontal aphasia and (2) behavioral disturbances ranging from irritability to a truly autistic response. These data seem to support the recently attributed role of the cerebellum as a modulator of the superior mental and social functions.     

Physiologically based cord clamping for infants ≥32+0 weeks gestation: A randomised clinical trial and reference percentiles for heart rate and oxygen saturation for infants ≥35+0 weeks gestation

BackgroundGlobally, the majority of newborns requiring resuscitation at birth are full term or late-preterm infants. These infants typically have their umbilical cord clamped early (ECC) before moving to a resuscitation platform, losing the potential support of the placental circulation. Physiologically based cord clamping (PBCC) is clamping the umbilical cord after establishing lung aeration and holds promise as a readily available means of improving early newborn outcomes. In mechanically ventilated lambs, PBCC improved cardiovascular stability and reduced hypoxia. We hypothesised that PBCC compared to ECC would result in higher heart rate (HR) in infants needing resuscitation, without compromising safety.Methods and findingsBetween 4 July 2018 and 18 May 2021, infants born at ≥32⁺⁰ weeks’ gestation with a paediatrician called to attend were enrolled in a parallel-arm randomised trial at 2 Australian perinatal centres. Following initial stimulation, infants requiring further resuscitation were randomised within 60 seconds of birth using a smartphone-accessible web link. The intervention (PBCC) was to establish lung aeration, either via positive pressure ventilation (PPV) or effective spontaneous breathing, prior to cord clamping. The comparator was early cord clamping (ECC) prior to resuscitation. The primary outcome was mean HR between 60 to 120 seconds after birth, measured using 3-lead electrocardiogram, extracted from video recordings blinded to group allocation. Nonrandomised infants had deferred cord clamping (DCC) ≥120 seconds in the observational study arm.Among 508 at-risk infants enrolled, 123 were randomised (n = 63 to PBCC, n = 60 to ECC). Median (interquartile range, IQR) for gestational age was 39.9 (38.3 to 40.7) weeks in PBCC infants and 39.6 (38.4 to 40.4) weeks in ECC infants. Approximately 49% and 50% of the PBCC and ECC infants were female, respectively. Five infants (PBCC = 2, ECC = 3, 4% total) had missing primary outcome data. Cord clamping occurred at a median (IQR) of 136 (126 to 150) seconds in the PBCC arm and 37 (27 to 51) seconds in the ECC arm. Mean HR between 60 to 120 seconds after birth was 154 bpm (beats per minute) for PBCC versus 158 bpm for ECC (adjusted mean difference −6 bpm, 95% confidence interval (CI) −17 to 5 bpm, P = 0.39). Among 31 secondary outcomes, postpartum haemorrhage ≥500 ml occurred in 34% and 32% of mothers in the PBCC and ECC arms, respectively. Two hundred ninety-five nonrandomised infants (55% female) with median (IQR) gestational age of 39.6 (38.6 to 40.6) weeks received DCC. Data from these infants was used to create percentile charts of expected HR and oxygen saturation in vigorous infants receiving DCC. The trial was limited by the small number of infants requiring prolonged or advanced resuscitation. PBCC may provide other important benefits we did not measure, including improved maternal–infant bonding and higher iron stores.ConclusionsIn this study, we observed that PBCC resulted in similar mean HR compared to infants receiving ECC. The findings suggest that for infants ≥32⁺⁰ weeks’ gestation who receive brief, effective resuscitation at closely monitored births, PBCC does not provide additional benefit over ECC (performed after initial drying and stimulation) in terms of key physiological markers of transition. PBCC was feasible using a simple, low-cost strategy at both cesarean and vaginal births. The percentile charts of HR and oxygen saturation may guide clinicians monitoring the transition of at-risk infants who receive DCC.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618000621213.

Shiraz Badurdeen and colleagues evaluate whether physiologically-based cord clamping provides physiological benefits over early cord clamping for infants requiring resuscitation at birth.     

Taking the bait: Developing a bait delivery system to target free‐ranging crocodiles and varanid lizards with a novel conservation strategy

In tropical Australia, conditioned taste aversion (CTA) can buffer vulnerable native predators from the invasion of a toxic prey species (cane toads, Rhinella marina). Thus, we need to develop methods to deploy aversion‐inducing baits in the field, in ways that maximize uptake by vulnerable species (but not other taxa). We constructed and field‐tested baiting devices, in situ with wild animals. Apparatus were set next to waterbodies and baited concurrently at multiple locations (over water, water''s edge, and on the bank). Baits were checked and replaced twice daily during the trial; remote cameras recorded visitation by native predators. Bait longevity was compared at sun‐exposed and shaded locations over 12 h. The strength required to remove baits from apparatus was measured in varanids and crocodiles. The device promoted high rates of bait uptake by freshwater crocodiles (47% baits consumed), varanid lizards (19% baits consumed), and non‐target taxa (34% baits consumed). Targeting specific predators can be achieved by manipulating bait location and time of deployment, as well as the force required to dislodge the bait. Crocodiles were best targeted with over‐water baits, whereas varanid lizards preferred baits located at the edges of waterbodies. When testing bait longevity in ambient conditions, during the daytime baits desiccated fully within 12 h, and faster in the sun than in the shade. Based on studies using captive animals, the “pulling force” strength of reptilian predators scaled with body size and was greater in crocodiles than in varanid lizards. We present the first conservation baiting protocol designed specifically for reptiles. Our results demonstrate the feasibility of widespread and taxon‐specific deployment of aversion‐inducing baits to buffer the impacts of invasive cane toads, and our methods are applicable (with modification) to other research and management programs globally.     

Antibody Specificities Associated with Neutralization Breadth in Plasma from Human Immunodeficiency Virus Type 1 Subtype C-Infected Blood Donors

Defining the specificities of the anti-human immunodeficiency virus type 1 (HIV-1) envelope antibodies able to mediate broad heterologous neutralization will assist in identifying targets for an HIV-1 vaccine. We screened 70 plasmas from chronically HIV-1-infected individuals for neutralization breadth. Of these, 16 (23%) were found to neutralize 80% or more of the viruses tested. Anti-CD4 binding site (CD4bs) antibodies were found in almost all plasmas independent of their neutralization breadth, but they mainly mediated neutralization of the laboratory strain HxB2 with little effect on the primary virus, Du151. Adsorption with Du151 monomeric gp120 reduced neutralizing activity to some extent in most plasma samples when tested against the matched virus, although these antibodies did not always confer cross-neutralization. For one plasma, this activity was mapped to a site overlapping the CD4-induced (CD4i) epitope and CD4bs. Anti-membrane-proximal external region (MPER) (r = 0.69; P < 0.001) and anti-CD4i (r = 0.49; P < 0.001) antibody titers were found to be correlated with the neutralization breadth. These anti-MPER antibodies were not 4E10- or 2F5-like but spanned the 4E10 epitope. Furthermore, we found that anti-cardiolipin antibodies were correlated with the neutralization breadth (r = 0.67; P < 0.001) and anti-MPER antibodies (r = 0.6; P < 0.001). Our study suggests that more than one epitope on the envelope glycoprotein is involved in the cross-reactive neutralization elicited during natural HIV-1 infection, many of which are yet to be determined, and that polyreactive antibodies are possibly involved in this phenomenon.The generation of an antibody response capable of neutralizing a broad range of viruses remains an important goal of human immunodeficiency virus type 1 (HIV-1) vaccine development. Despite multiple efforts in the design of immunogens capable of inducing such humoral responses, little progress has been made (18, 20, 39). The sequence variability of the virus, as well as masking mechanisms exhibited by the envelope glycoprotein, has further hindered this pursuit (6, 22). It is known that while the majority of HIV-infected individuals mount a strong neutralization response against their own virus within the first 6 to 12 months of infection, breadth is observed in only a few individuals years later (5, 10, 15, 26, 33, 40, 41). However, very little is known about the specificities of the antibodies that confer this broad cross-neutralization. It is plausible that broadly cross-neutralizing (BCN) plasmas contain antibodies that target conserved regions of the envelope glycoprotein, as exemplified by a number of well-characterized broadly neutralizing monoclonal antibodies (MAbs). The b12 MAb recognizes the CD4 binding site (CD4bs), and 2G12 binds to surface glycans (7, 42, 44, 56). The 447-52D MAb recognizes the V3 loop, and 17b, E51, and 412d bind to CD4-induced (CD4i) epitopes that form part of the coreceptor binding site (13, 21, 51, 54). Finally, the MAbs 2F5, 4E10, and Z13e1 recognize distinct linear sequences in the gp41 membrane-proximal external region (MPER) (36, 57). The targets of these neutralizing MAbs provide a rational starting point for examining the complex nature of polyclonal plasma samples.Several groups have addressed the need to develop methodologies to elucidate the presence of certain neutralizing-antibody specificities (1, 8, 9, 29, 30, 43, 55). A number of these studies reported that the BCN antibodies in plasma can in some cases be adsorbed using gp120 immobilized on beads (1, 9, 29, 30, 43). Furthermore, the activities of some of these anti-gp120 neutralizing antibodies could be mapped to the CD4bs, as the D368R mutant gp120 failed to adsorb them (1, 29, 30, 43).Antibodies to CD4i epitopes are frequently found in HIV-1-infected individuals and are thought to primarily target the coreceptor binding site, which includes the bridging sheet and possibly parts of the V3 region. Decker and colleagues (8) showed that MAbs to HIV-1 CD4i epitopes can neutralize HIV-2 when pretreated with soluble CD4 (sCD4), indicating that the CD4i epitope is highly conserved among different HIV lineages. The poor accessibility of CD4i epitopes, however, has precluded this site from being a major neutralizing-antibody target (24), although a recent study suggested that some of the cross-neutralizing activity in polyclonal sera mapped to a CD4i epitope (30).Another site that has attracted considerable attention as a target for cross-neutralizing antibodies is the MPER, a linear stretch of 34 amino acids in gp41. Anti-MPER antibodies have been detected in the plasma of HIV-infected individuals by using chimeric viruses with HIV-1 MPER grafted into a simian immunodeficiency virus or an HIV-2 envelope glycoprotein (15, 55). These studies concluded that 2F5- and 4E10-like antibodies were rarely found in HIV-1-infected plasmas; however, other specificities within the MPER were recognized by around one-third of HIV-1-infected individuals (15). More recently, 4E10-like and 2F5-like antibodies (30, 43), as well as antibodies to novel epitopes within the MPER (1), have been shown to be responsible for neutralization breadth in a small number of plasma samples. The anti-MPER MAb 4E10 has been shown to react to autoantigens, leading to the suggestion that their rarity in human infection is due to the selective deletion of B cells with these specificities (17, 35). Furthermore, a recent study found an association between anti-MPER and anti-cardiolipin (CL) antibodies, although an association with neutralization was not examined (31).A recent study by Binley and coworkers used an array of methodologies to determine the antibody specificities present in subtype B and subtype C plasma samples with neutralization breadth (1). While antibodies to gp120, some of which mapped to the CD4bs, and to MPER were identified, most of the neutralizing activity in the BCN plasma could not be attributed to any of the known conserved envelope epitopes. Furthermore, it is not clear how common these specificities are among HIV-1-positive plasmas and whether they are only associated with BCN activity.In this study, we investigated a large collection of HIV-1-infected plasmas obtained from the South African National Blood Services. We aimed to determine if there is a relationship between the presence of certain antibody specificities, such as those against CD4i epitopes, MPER, or the CD4bs, and the neutralizing activities present in these plasmas. Furthermore, we evaluated the presence of various autoreactive antibodies and analyzed whether they might be associated with neutralization breadth.     

Data mining in proteomic mass spectrometry

Data mining application to proteomic data from mass spectrometry has gained much interest in recent years. Advances made in proteomics and mass spectrometry have resulted in considerable amount of data that cannot be easily visualized or interpreted. Mass spectral proteomic datasets are typically high dimensional but with small sample size. Consequently, advanced artificial intelligence and machine learning algorithms are increasingly being used for knowledge discovery from such datasets. Their overall goal is to extract useful information that leads to the identification of protein biomarker candidates. Such biomarkers could potentially have diagnostic value as tools for early detection, diagnosis, and prognosis of many diseases. The purpose of this review is to focus on the current trends in mining mass spectral proteomic data. Special emphasis is placed on the critical steps involved in the analysis of surface-enhanced laser desorption/ionization mass spectrometry proteomic data. Examples are drawn from previously published studies and relevant data mining terminology and techniques are exlained.     

A review of the occurrence of inter‐colony segregation of seabird foraging areas and the implications for marine environmental impact assessment

Understanding the determinants of species’ distributions is a fundamental aim in ecology and a prerequisite for conservation but is particularly challenging in the marine environment. Advances in bio‐logging technology have resulted in a rapid increase in studies of seabird movement and distribution in recent years. Multi‐colony studies examining the effects of intra‐ and inter‐colony competition on distribution have found that several species exhibit inter‐colony segregation of foraging areas, rather than overlapping distributions. These findings are timely given the increasing rate of human exploitation of marine resources and the need to make robust assessments of likely impacts of proposed marine developments on biodiversity. Here we review the occurrence of foraging area segregation reported by published tracking studies in relation to the density‐dependent hinterland (DDH) model, which predicts that segregation occurs in response to inter‐colony competition, itself a function of colony size, distance from the colony and prey distribution. We found that inter‐colony foraging area segregation occurred in 79% of 39 studies. The frequency of occurrence was similar across the four seabird orders for which data were available, and included species with both smaller (10–100 km) and larger (100–1000 km) foraging ranges. Many predictions of the DDH model were confirmed, with examples of segregation in response to high levels of inter‐colony competition related to colony size and proximity, and enclosed landform restricting the extent of available habitat. Moreover, as predicted by the DDH model, inter‐colony overlap tended to occur where birds aggregated in highly productive areas, often remote from all colonies. The apparent prevalence of inter‐colony foraging segregation has important implications for assessment of impacts of marine development on protected seabird colonies. If a development area is accessible from multiple colonies, it may impact those colonies much more asymmetrically than previously supposed. Current impact assessment approaches that do not consider spatial inter‐colony segregation will therefore be subject to error. We recommend the collection of tracking data from multiple colonies and modelling of inter‐colony interactions to predict colony‐specific distributions.     

Leishmania braziliensis:Characterisation of a Complex Specific Subtelomeric Repeat Sequence and Its Use in the Detection of Parasites

Fu, G., Perona-Wright, G., and Barker, D. C. 1998.Leishmania braziliensis: Characterisation of a complex specific subtelomeric repeat sequence and its use in the detection of parasites.Experimental Parasitology90, 236–243. A 1.6-kb tandem repeat sequence had previously been identified in the subtelomeric region of mini- and megabase chromosomes fromLeishmania braziliensis.Southern hybridisation was used to demonstrate that the repeat is complex specific. The sequence was characterised in strains representing four species of theL. braziliensiscomplex. This data allowed an assessment of the evolutionary relationship of the four species. PCR primers targeted to the repeat amplify only DNA from species of theL. braziliensiscomplex. Titration assays indicate that a minimum of 50 fg of parasite DNA can be detected by PCR alone. Southern hybridisation increases the limit of detection to 5 fg. Interspecies variation in the repeat sequence enabled restriction enzyme digestion of PCR products to distinguish individual species within theL. braziliensiscomplex.     

Meals on Wheels? A Decade of Megafaunal Visual and Acoustic Observations from Offshore Oil & Gas Rigs and Platforms in the North and Irish Seas

A decade of visual and acoustic detections of marine megafauna around offshore Oil & Gas (O&G) installations in the North and Irish Seas are presented. Marine megafauna activity was monitored visually and acoustically by Joint Nature Conservation Committee (JNCC) qualified and experienced Marine Mammal Observers (MMO) and Passive Acoustic Monitoring (PAM) Operators respectively, with real-time towed PAM in combination with industry standard software, PAMGuard. Monitoring was performed during routine O&G industrial operations for underwater noise mitigation purposes, and to ensure adherence to regulatory guidelines. Incidental sightings by off-effort MMOs and installation crew were also reported. Visual and acoustic monitoring spanned 55 non-consecutive days between 2004 and 2014. A total of 47 marine mammal sightings were recorded by MMOs on dedicated watch, and 10 incidental sightings of marine megafauna were reported over 10 years. Species included: harbour porpoise (Phocoena phocoena), Atlantic white-sided dolphin (Lagenorhynchus acutus), white beaked dolphin (Lagenorhynchus albirostris), common dolphin (Delphinus delphis), minke whale (Balaenoptera acutorostrata), common seal (Phoca vitulina), grey seal (Halichoerus grypus) and, basking shark (Cetorhinus maximus). Passive Acoustic Monitoring was conducted on two occasions in 2014; 160 PAM hours over 12 days recorded a total of 308 individual clicks identified as harbour porpoises. These appear to be the first such acoustic detections obtained from a North Sea drilling rig whilst using a typically configured hydrophone array designed for towing in combination with real-time PAMGuard software. This study provides evidence that marine megafauna are present around mobile and stationary offshore O&G installations during routine operational activities. On this basis, Environmental Impact Assessments (EIAs) for decommissioning O&G platforms should be carried-out on a case-by-case basis, and must include provisions for hitherto overlooked marine megafauna.