A morphological model for sexing nestling peregrine falcons (Falco Peregrinus Macropus) verified through genetic analysis

Adult peregrine falcons (Falco peregrinus macropus) have monotypic plumage and display strong reversed sexual dimorphism, with females significantly larger than males. Reversed sexual dimorphism is measurable among nestlings in the latter stages of their development and can therefore be used to differentiate between sexes. In the early stages of development, however, nestlings cannot be sexed with any degree of certainty because morphological differentiation between the sexes is not well developed. During this study we developed a model for sexing younger nestlings based on genetic analysis and morphometric data collected as part of a long-term banding study of this species. A discriminant function model based on morphological characteristics was developed for determining the sex of nestlings (n = 150) in the field and was shown to be 96.0% accurate. This predictive model was further tested against an independent morphometric dataset taken from a second group of nestlings (n = 131). The model correctly allocated sex to 96.2% of this second group of nestlings. Sex can reliably be determined (98.6% accurate) for nestlings that have a wing length of at least 9 cm using this model. Application of this model, therefore, allows the banding of younger nestlings and, as such, significantly increases the period of time over which banding can occur. Another important implication of this model is that by banding nestlings earlier, they are less likely to jump from the nest, therefore reducing the risk of injury to both the brood and the bander.<br /

The challenges of COVID-19 for people with dementia with Lewy bodies and family caregivers.

Introduction During the current SARS-CoV-2 pandemic dementia has been identified as disproportionally common in adults aged over 65 who develop severe COVID-19.1 Observational data from the International Severe Acute Respiratory and Emerging Infections Consortium also confirms a high prevalence of dementia in older adults hospitalised with COVID-19.2 It is so far unclear whether there is any direct effect of dementia pathologies as dementia is a disease of old age, and thus likely to be associated with a variety of comorbidities, in particular, frailty, which may further exacerbate the risk of severe infection. In addition up to one third of COVID patients have demonstrated neurological sequelae3 and there may be both direct (viral infection within the brain, vascular effects) and indirect effects (e.g. host immunological response, impact of treatment) of SARS-CoV-2 on the brain.4 It is therefore possible that SARS-CoV-2 infection may accentuate any pre-existing neurodegenerative disease

Observations and Implications of the Star Formation History of the LMC

We present derivations of star formation histories based on color-magnitude diagrams of three fields in the LMC from HST/WFPC2 observations. A significant component of stars older than 4 Gyr is required to match the observed color-magnitude diagrams. Models with a dispersion-free age-metallicity relation are unable to reproduce the width of the observed main sequence; models with a range of metallicity at a given age provide a much better fit. Such models allow us to construct complete ``population boxes'' for the LMC based entirely on color-magnitude diagrams; remarkably, these qualitatively reproduce the age-metallicity relation observed in LMC clusters. We discuss some of the uncertainties in deriving star formation histories. We find, independently of the models, that the LMC bar field has a larger relative component of older stars than the outer fields. The main implications suggested by this study are: 1) the star formation history of field stars appears to differ from the age distribution of clusters, 2) there is no obvious evidence for bursty star formation, but our ability to measure bursts shorter in duration than $\sim$ 25% of any given age is limited by the statistics of the observed number of stars, 3) there may be some correlation of the star formation rate with the last close passage of the LMC/SMC/Milky Way, but there is no dramatic effect, and 4) the derived star formation history is probably consistent with observed abundances, based on recent chemical evolution models.Comment: Accepted by AJ, 36 pages including 12 figure

Cholera hotspots and surveillance constraints contributing to recurrent epidemics in Tanzania

Objective: We described the dynamics of cholera in Tanzania between 2007 and 2017 and assessed the weaknesses of the current surveillance system in providing necessary data in achieving the global roadmap to 2030 for cholera control. Results: The Poisson-based spatial scan identifed cholera hotspots in mainland Tanzania. A zero-infated Poisson regression investigated the relationship between the incidence of cholera and available demographic, socio-economic and climatic exposure variables. Four cholera hotspots were detected covering 17 regions, home to 28 million people, including the central regions and those surrounding the Lakes Victoria, Tanganyika and Nyaza. The risk of experiencing cholera in these regions was up to 2.9 times higher than elsewhere in the country. Regression analyses revealed that every 100 km of water perimeter in a region increased the cholera incidence by 1.5%. Due to the compilation of surveillance data at regional level rather than at district, we were unable to reliably identify any other signifcant risk factors and specifc hotspots. Cholera high-risk populations in Tanzania include those living near lakes and central regions. Successful surveillance require disaggregated data available weekly and at district levels in order to serve as data for action to support the roadmap for cholera control.Published versio

ANTIBACTERIAL EFFECTS OF SINGLE AND COMBINED CRUDE EXTRACTS OF SYNADENIUM GLAUCESCENS AND COMMIPHORA SWYNNERTONII

Background: Synadenium glaucescens and Commiphora swynnertonii are among the reported plants used traditionally for treatment of bacterial infections. This study reports antibacterial effects of single and combined extracts from leaves, stem and root barks of Commiphora swynnertonii and Synadenium glaucescens. Materials and Methods: Plants were collected from Manyara and Njombe regions in Tanzania. Extraction was done using dichloromethane and methanol. The extracts were assessed for antibacterial activity against Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis) and Gram-negative bacteria (Escherichia coli, Klebsiella pneumonia and Pseudomonas aeruginosa). Minimum Inhibitory Concentrations (MIC) was determined by broth microdilution, while Fractional Inhibitory Concentration (FIC) indices were calculated from MIC values of combined extracts to determine combination effects. Results: Strong antibacterial activities were demonstrated by all extracts of S. glaucescens (MIC 0.011-0.375mg/mL) against Gram-positive bacteria and methanol extracts of C. swynnertonii (MIC 0.047-0.375mg/mL). Synergistic effect was observed when combining methanol extracts of C. swynnertonii stem bark with S. glaucescens leaves against S. aureus (∑FIC 0.5), Other synergistic effects were observed against E. faecalis with dichloromethane extracts of C. swynnertonii stem bark and S. glaucescens stem bark (∑FIC 0.5), and C. swynnertonii root bark and S. glaucescens root bark (FIC index 0.3). For the remaining combinations, mainly additive effects were observed. Conclusion: Synergistic effects on bacteria were observed by combining different plant parts of S. glaucescens and C. swynnertonii suggesting that it could be beneficial to combine such extracts when used for antibacterial purposes

Search for a Solution of the Pioneer Anomaly

In 1972 and 1973 the Pioneer 10 and 11 missions were launched. They were the first to explore the outer solar system and achieved stunning breakthroughs in deep-space exploration. But beginning in about 1980 an unmodeled force of \sim 8 \times 10^{-8} cm/s^2, directed approximately towards the Sun, appeared in the tracking data. It later was unambiguously verified as being in the data and not an artifact. The cause remains unknown (although radiant heat remains a likely origin). With time more and more effort has gone into understanding this anomaly (and also possibly related effects). We review the situation and describe ongoing programs to resolve the issue.Comment: 24 pages 8 figure

Evolution of the leukotoxin promoter in genus Mannheimia

&lt;b&gt;Background&lt;/b&gt;: The &lt;i&gt;Mannheimia&lt;/i&gt; species encompass a wide variety of bacterial lifestyles, including opportunistic pathogens and commensals of the ruminant respiratory tract, commensals of the ovine rumen, and pathogens of the ruminant integument. Here we present a scenario for the evolution of the leukotoxin promoter among representatives of the five species within genus &lt;i&gt;Mannheimia&lt;/i&gt;. We also consider how the evolution of the leukotoxin operon fits with the evolution and maintenance of virulence. &lt;b&gt;Results&lt;/b&gt;: The alignment of the intergenic regions upstream of the leukotoxin genes showed significant sequence and positional conservation over a 225-bp stretch immediately proximal to the transcriptional start site of the &lt;i&gt;lktC&lt;/i&gt; gene among all &lt;i&gt;Mannheimia&lt;/i&gt; strains. However, in the course of the &lt;i&gt;Mannheimia&lt;/i&gt; genome evolution, the acquisition of individual noncoding regions upstream of the conserved promoter region has occurred. The rate of evolution estimated branch by branch suggests that the conserved promoter may be affected to different extents by the types of natural selection that potentially operate in regulatory regions. Tandem repeats upstream of the core promoter were confined to &lt;i&gt;M. haemolytica&lt;/i&gt; with a strong association between the sequence of the repeat units, the number of repeat units per promoter, and the phylogenetic history of this species. &lt;b&gt;Conclusion&lt;/b&gt;: The mode of evolution of the intergenic regions upstream of the leukotoxin genes appears to be highly dependent on the lifestyle of the bacterium. Transition from avirulence to virulence has occurred at least once in &lt;i&gt;M. haemolytica&lt;/i&gt; with some evolutionary success of bovine serotype A1/A6 strains. Our analysis suggests that changes in &lt;i&gt;cis&lt;/i&gt;-regulatory systems have contributed to the derived virulence phenotype by allowing phase-variable expression of the leukotoxin protein. We propose models for how phase shifting and the associated virulence could facilitate transmission to the nasopharynx of new hosts

GABAA receptors in GtoPdb v.2023.1

The GABAA receptor is a ligand-gated ion channel of the Cys-loop family that includes the nicotinic acetylcholine, 5-HT3 and strychnine-sensitive glycine receptors. GABAA receptor-mediated inhibition within the CNS occurs by fast synaptic transmission, sustained tonic inhibition and temporally intermediate events that have been termed 'GABAA, slow' [45]. GABAA receptors exist as pentamers of 4TM subunits that form an intrinsic anion selective channel. Sequences of six &#945;, three &#946;, three &#947;, one &#948;, three &#961;, one &#949;, one &#960; and one &#952; GABAA receptor subunits have been reported in mammals [281, 237, 238, 288]. The &#960;-subunit is restricted to reproductive tissue. Alternatively spliced versions of many subunits exist (e.g. &#945;4- and &#945;6- (both not functional) &#945;5-, &#946;2-, &#946;3- and &#947;2), along with RNA editing of the &#945;3 subunit [71]. The three &#961;-subunits, (&#961;1-3) function as either homo- or hetero-oligomeric assemblies [365, 50]. Receptors formed from &#961;-subunits, because of their distinctive pharmacology that includes insensitivity to bicuculline, benzodiazepines and barbiturates, have sometimes been termed GABAC receptors [365], but they are classified as GABAA receptors by NC-IUPHAR on the basis of structural and functional criteria [16, 237, 238].Many GABAA receptor subtypes contain &#945;-, &#946;- and &#947;-subunits with the likely stoichiometry 2&#945;.2&#946;.1&#947; [170, 237]. It is thought that the majority of GABAA receptors harbour a single type of &#945;- and &#946; -subunit variant. The &#945;1&#946;2&#947;2 hetero-oligomer constitutes the largest population of GABAA receptors in the CNS, followed by the &#945;2&#946;3&#947;2 and &#945;3&#946;3&#947;2 isoforms. Receptors that incorporate the &#945;4- &#945;5-or &#945;6-subunit, or the &#946;1-, &#947;1-, &#947;3-, &#948;-, &#949;- and &#952;-subunits, are less numerous, but they may nonetheless serve important functions. For example, extrasynaptically located receptors that contain &#945;6- and &#948;-subunits in cerebellar granule cells, or an &#945;4- and &#948;-subunit in dentate gyrus granule cells and thalamic neurones, mediate a tonic current that is important for neuronal excitability in response to ambient concentrations of GABA [211, 275, 84, 19, 293]. GABA binding occurs at the &#946;+/&#945;- subunit interface and the homologous &#947;+/&#945;- subunits interface creates the benzodiazepine site. A second site for benzodiazepine binding has recently been postulated to occur at the &#945;+/&#946;- interface ([257]; reviewed by [287]). The particular &#945;-and &#947;-subunit isoforms exhibit marked effects on recognition and/or efficacy at the benzodiazepine site. Thus, receptors incorporating either &#945;4- or &#945;6-subunits are not recognised by &#8216;classical&#8217; benzodiazepines, such as flunitrazepam (but see [362]). The trafficking, cell surface expression, internalisation and function of GABAA receptors and their subunits are discussed in detail in several recent reviews [52, 141, 190, 322] but one point worthy of note is that receptors incorporating the &#947;2 subunit (except when associated with &#945;5) cluster at the postsynaptic membrane (but may distribute dynamically between synaptic and extrasynaptic locations), whereas those incorporating the &#948; subunit appear to be exclusively extrasynaptic. NC-IUPHAR [16, 237, 3, 2] class the GABAA receptors according to their subunit structure, pharmacology and receptor function. Currently, eleven native GABAA receptors are classed as conclusively identified (i.e., &#945;1&#946;2&#947;2, &#945;2&#946;&#947;2, &#945;3&#946;&#947;2, &#945;4&#946;&#947;2, &#945;4&#946;2&#948;, &#945;4&#946;3&#948;, &#945;5&#946;&#947;2, &#945;6&#946;&#947;2, &#945;6&#946;2&#948;, &#945;6&#946;3&#948; and &#961;) with further receptor isoforms occurring with high probability, or only tentatively [237, 238]. It is beyond the scope of this Guide to discuss the pharmacology of individual GABAA receptor isoforms in detail; such information can be gleaned in the reviews [16, 96, 170, 175, 144, 281, 218, 237, 238, 284, 9, 10]. Agents that discriminate between &#945;-subunit isoforms are noted in the table and additional agents that demonstrate selectivity between receptor isoforms, for example via &#946;-subunit selectivity, are indicated in the text below. The distinctive agonist and antagonist pharmacology of &#961; receptors is summarised in the table and additional aspects are reviewed in [365, 50, 146, 225].Several high-resolution cryo-electron microscopy structures have been described in which the full-length human &#945;1&#946;3&#947;2L GABAA receptor in lipid nanodiscs is bound to the channel-blocker picrotoxin, the competitive antagonist bicuculline, the agonist GABA (&#947;-aminobutyric acid), and the classical benzodiazepines alprazolam and diazepam [200]

GABAA receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

The GABAA receptor is a ligand-gated ion channel of the Cys-loop family that includes the nicotinic acetylcholine, 5-HT3 and strychnine-sensitive glycine receptors. GABAA receptor-mediated inhibition within the CNS occurs by fast synaptic transmission, sustained tonic inhibition and temporally intermediate events that have been termed &#8216;GABAA, slow&#8217; [41]. GABAA receptors exist as pentamers of 4TM subunits that form an intrinsic anion selective channel. Sequences of six &#945;, three &#946;, three &#947;, one &#948;, three &#961;, one &#949;, one &#960; and one &#952; GABAA receptor subunits have been reported in mammals [273, 232, 231, 278]. The &#960;-subunit is restricted to reproductive tissue. Alternatively spliced versions of many subunits exist (e.g. &#945;4- and &#945;6- (both not functional) &#945;5-, &#946;2-, &#946;3- and &#947;2), along with RNA editing of the &#945;3 subunit [67]. The three &#961;-subunits, (&#961;1-3) function as either homo- or hetero-oligomeric assemblies [354, 46]. Receptors formed from &#961;-subunits, because of their distinctive pharmacology that includes insensitivity to bicuculline, benzodiazepines and barbiturates, have sometimes been termed GABAC receptors [354], but they are classified as GABAA receptors by NC-IUPHAR on the basis of structural and functional criteria [14, 232, 231].Many GABAA receptor subtypes contain &#945;-, &#946;- and &#947;-subunits with the likely stoichiometry 2&#945;.2&#946;.1&#947; [164, 232]. It is thought that the majority of GABAA receptors harbour a single type of &#945;- and &#946; -subunit variant. The &#945;1&#946;2&#947;2 hetero-oligomer constitutes the largest population of GABAA receptors in the CNS, followed by the &#945;2&#946;3&#947;2 and &#945;3&#946;3&#947;2 isoforms. Receptors that incorporate the &#945;4- &#945;5-or &#945;6-subunit, or the &#946;1-, &#947;1-, &#947;3-, &#948;-, &#949;- and &#952;-subunits, are less numerous, but they may nonetheless serve important functions. For example, extrasynaptically located receptors that contain &#945;6- and &#948;-subunits in cerebellar granule cells, or an &#945;4- and &#948;-subunit in dentate gyrus granule cells and thalamic neurones, mediate a tonic current that is important for neuronal excitability in response to ambient concentrations of GABA [205, 268, 79, 17, 283]. GABA binding occurs at the &#946;+/&#945;- subunit interface and the homologous &#947;+/&#945;- subunits interface creates the benzodiazepine site. A second site for benzodiazepine binding has recently been postulated to occur at the &#945;+/&#946;- interface ([250]; reviewed by [277]). The particular &#945;-and &#947;-subunit isoforms exhibit marked effects on recognition and/or efficacy at the benzodiazepine site. Thus, receptors incorporating either &#945;4- or &#945;6-subunits are not recognised by &#8216;classical&#8217; benzodiazepines, such as flunitrazepam (but see [351]). The trafficking, cell surface expression, internalisation and function of GABAA receptors and their subunits are discussed in detail in several recent reviews [48, 136, 184, 311] but one point worthy of note is that receptors incorporating the &#947;2 subunit (except when associated with &#945;5) cluster at the postsynaptic membrane (but may distribute dynamically between synaptic and extrasynaptic locations), whereas as those incorporating the d subunit appear to be exclusively extrasynaptic. NC-IUPHAR [14, 232] class the GABAA receptors according to their subunit structure, pharmacology and receptor function. Currently, eleven native GABAA receptors are classed as conclusively identified (i.e., &#945;1&#946;2&#947;2, &#945;1&#946;&#947;2, &#945;3&#946;&#947;2, &#945;4&#946;&#947;2, &#945;4&#946;2&#948;, &#945;4&#946;3&#948;, &#945;5&#946;&#947;2, &#945;6&#946;&#947;2, &#945;6&#946;2&#948;, &#945;6&#946;3&#948; and &#961;) with further receptor isoforms occurring with high probability, or only tentatively [232, 231]. It is beyond the scope of this Guide to discuss the pharmacology of individual GABAA receptor isoforms in detail; such information can be gleaned in the reviews [14, 91, 164, 169, 140, 273, 212, 232, 231] and [8, 7]. Agents that discriminate between &#945;-subunit isoforms are noted in the table and additional agents that demonstrate selectivity between receptor isoforms, for example via &#946;-subunit selectivity, are indicated in the text below. The distinctive agonist and antagonist pharmacology of &#961; receptors is summarised in the table and additional aspects are reviewed in [354, 46, 141, 219].Several high-resolution cryo-electron microscopy structures have been described in which the full-length human &#945;1&#946;3&#947;2L GABAA receptor in lipid nanodiscs is bound to the channel-blocker picrotoxin, the competitive antagonist bicuculline, the agonist GABA (&#947;-aminobutyric acid), and the classical benzodiazepines alprazolam and diazepam [194]

GABAA receptors in GtoPdb v.2021.3

The GABAA receptor is a ligand-gated ion channel of the Cys-loop family that includes the nicotinic acetylcholine, 5-HT3 and strychnine-sensitive glycine receptors. GABAA receptor-mediated inhibition within the CNS occurs by fast synaptic transmission, sustained tonic inhibition and temporally intermediate events that have been termed 'GABAA, slow' [45]. GABAA receptors exist as pentamers of 4TM subunits that form an intrinsic anion selective channel. Sequences of six &#945;, three &#946;, three &#947;, one &#948;, three &#961;, one &#949;, one &#960; and one &#952; GABAA receptor subunits have been reported in mammals [278, 235, 236, 283]. The &#960;-subunit is restricted to reproductive tissue. Alternatively spliced versions of many subunits exist (e.g. &#945;4- and &#945;6- (both not functional) &#945;5-, &#946;2-, &#946;3- and &#947;2), along with RNA editing of the &#945;3 subunit [71]. The three &#961;-subunits, (&#961;1-3) function as either homo- or hetero-oligomeric assemblies [359, 50]. Receptors formed from &#961;-subunits, because of their distinctive pharmacology that includes insensitivity to bicuculline, benzodiazepines and barbiturates, have sometimes been termed GABAC receptors [359], but they are classified as GABAA receptors by NC-IUPHAR on the basis of structural and functional criteria [16, 235, 236].Many GABAA receptor subtypes contain &#945;-, &#946;- and &#947;-subunits with the likely stoichiometry 2&#945;.2&#946;.1&#947; [168, 235]. It is thought that the majority of GABAA receptors harbour a single type of &#945;- and &#946; -subunit variant. The &#945;1&#946;2&#947;2 hetero-oligomer constitutes the largest population of GABAA receptors in the CNS, followed by the &#945;2&#946;3&#947;2 and &#945;3&#946;3&#947;2 isoforms. Receptors that incorporate the &#945;4- &#945;5-or &#945;6-subunit, or the &#946;1-, &#947;1-, &#947;3-, &#948;-, &#949;- and &#952;-subunits, are less numerous, but they may nonetheless serve important functions. For example, extrasynaptically located receptors that contain &#945;6- and &#948;-subunits in cerebellar granule cells, or an &#945;4- and &#948;-subunit in dentate gyrus granule cells and thalamic neurones, mediate a tonic current that is important for neuronal excitability in response to ambient concentrations of GABA [209, 272, 83, 19, 288]. GABA binding occurs at the &#946;+/&#945;- subunit interface and the homologous &#947;+/&#945;- subunits interface creates the benzodiazepine site. A second site for benzodiazepine binding has recently been postulated to occur at the &#945;+/&#946;- interface ([254]; reviewed by [282]). The particular &#945;-and &#947;-subunit isoforms exhibit marked effects on recognition and/or efficacy at the benzodiazepine site. Thus, receptors incorporating either &#945;4- or &#945;6-subunits are not recognised by &#8216;classical&#8217; benzodiazepines, such as flunitrazepam (but see [356]). The trafficking, cell surface expression, internalisation and function of GABAA receptors and their subunits are discussed in detail in several recent reviews [52, 140, 188, 316] but one point worthy of note is that receptors incorporating the &#947;2 subunit (except when associated with &#945;5) cluster at the postsynaptic membrane (but may distribute dynamically between synaptic and extrasynaptic locations), whereas as those incorporating the &#948; subunit appear to be exclusively extrasynaptic. NC-IUPHAR [16, 235, 3, 2] class the GABAA receptors according to their subunit structure, pharmacology and receptor function. Currently, eleven native GABAA receptors are classed as conclusively identified (i.e., &#945;1&#946;2&#947;2, &#945;1&#946;&#947;2, &#945;3&#946;&#947;2, &#945;4&#946;&#947;2, &#945;4&#946;2&#948;, &#945;4&#946;3&#948;, &#945;5&#946;&#947;2, &#945;6&#946;&#947;2, &#945;6&#946;2&#948;, &#945;6&#946;3&#948; and &#961;) with further receptor isoforms occurring with high probability, or only tentatively [235, 236]. It is beyond the scope of this Guide to discuss the pharmacology of individual GABAA receptor isoforms in detail; such information can be gleaned in the reviews [16, 95, 168, 173, 143, 278, 216, 235, 236] and [9, 10]. Agents that discriminate between &#945;-subunit isoforms are noted in the table and additional agents that demonstrate selectivity between receptor isoforms, for example via &#946;-subunit selectivity, are indicated in the text below. The distinctive agonist and antagonist pharmacology of &#961; receptors is summarised in the table and additional aspects are reviewed in [359, 50, 145, 223].Several high-resolution cryo-electron microscopy structures have been described in which the full-length human &#945;1&#946;3&#947;2L GABAA receptor in lipid nanodiscs is bound to the channel-blocker picrotoxin, the competitive antagonist bicuculline, the agonist GABA (&#947;-aminobutyric acid), and the classical benzodiazepines alprazolam and diazepam [198]