86,746 research outputs found

    NEW ROLES FOR FC RECEPTORS IN NEURODEGENERATION-THE IMPACT ON IMMUNOTHERAPY FOR ALZHEIMER’S DISEASE

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    There are an estimated 18 million Alzheimer’s disease (AD) sufferers worldwide and with no disease modifying treatment currently available, development of new therapies represents an enormous unmet clinical need. AD is characterised by episodic memory loss followed by severe cognitive decline and is associated with many neuropathological changes. AD is characterised by deposits of amyloid beta (Aβ), neurofibrillary tangles, and neuroinflammation. Active immunisation or passive immunisation against Aβ leads to the clearance of deposits in transgenic mice expressing human Aβ. This clearance is associated with reversal of associated cognitive deficits, but these results have failed to translate to humans, with both active and passive immunotherapy failing to improve memory loss. One explanation for these observations is that certain anti-Aβ antibodies mediate damage to the cerebral vasculature limiting the top dose and potentially reducing efficacy. Fc gamma receptors (Fcγ) are a family of immunoglobulin like receptors which bind to the Fc portion of IgG, and mediate the response of effector cells to immune complexes. Data from both mouse and human studies suggest that cross-linking Fc receptors by therapeutic antibodies and the subsequent pro-inflammatory response mediates the vascular side effects seen following immunotherapy. Increasing evidence is emerging that Fc receptor expression on CNS resident cells, including microglia and neurons, is increased during aging and functionally involved in the pathogenesis of age-related neurodegenerative diseases. We propose that increased expression and ligation of Fc receptors in the CNS, either by endogenous IgG or therapeutic antibodies, has the potential to induce vascular damage and exacerbate neurodegeneration. To produce safe and effective immunotherapies for AD and other neurodegenerative diseases it will be vital to understand the role of Fc receptors in the healthy and diseased brain

    Microglia and macrophages of the central nervous system: the contribution of microglia priming and systemic inflammation to chronic neurodegeneration

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    Microglia, the resident immune cells of the central nervous system (CNS), play an important role in CNS homeostasis during development, adulthood and ageing. Their phenotype and function have been widely studied, but most studies have focused on their local interactions in the CNS. Microglia are derived from a particular developmental niche, are long-lived, locally replaced and form a significant part of the communication route between the peripheral immune system and the CNS; all these components of microglia biology contribute to maintaining homeostasis. Microglia function is tightly regulated by the CNS microenvironment, and increasing evidence suggests that disturbances, such as neurodegeneration and ageing, can have profound consequences for microglial phenotype and function. We describe the possible biological mechanisms underlying the altered threshold for microglial activation, also known as 'microglial priming', seen in CNS disease and ageing and consider how priming may contribute to turning immune-to-brain communication from a homeostatic pathway into a maladaptive response that contributes to symptoms and progression of diseases of the CNS

    Long term impact of systemic bacterial infection on the cerebral vasculature and microglia

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    Background: Systemic infection leads to generation of inflammatory mediators that result in metabolic and behavioural changes. Repeated or chronic systemic inflammation leads to a state of innate immune tolerance: a protective mechanism against over-activity of the immune system. In this study we investigated the immune adaptation of microglia and brain vascular endothelial cells in response to systemic inflammation or bacterial infection. Methods: Mice were given repeated doses of lipopolysaccharide (LPS) or a single injection of live Salmonella typhimurium. Inflammatory cytokines were measured in serum, spleen and brain, and microglial phenotype studied by immunohistochemistry.mice were infected with Salmonella typhimurium and subsequently challenged with a focal unilateral, intracerebral injection of LPS. Results: Repeated systemic LPS challenges resulted in increased brain IL-1?, TNF? and IL-12 levels, despite attenuated systemic cytokine production. Each LPS challenge induced significant changes in burrowing behaviour. In contrast, brain IL-1? and IL-12 levels in Salmonella typhimurium infected mice increased over three weeks, with high interferon-? levels in the circulation. Behavioural changes were only observed during the acute phase of the infection. Microglia and cerebral vasculature display an activated phenotype, and focal intracerebral injection of LPS 4 weeks after infection results in an exaggerated local inflammatory response when compared to non-infected mice. Conclusions: These studies reveal that the innate immune cells in the brain do not become tolerant to systemic infection, but are primed instead. This may lead to prolonged and damaging cytokine production that may have aprofound effect on the onset and/ or progression of pre-existing neurodegenerative disease.Humans and animals are regularly exposed to bacterial and viral pathogens that can have a considerable impact on our day-to-day living [1]. Upon infection, a set of immune, physiological, metabolic, and behavioural responses is initiated, representing a highly organized strategy of the organism to fight infection. Pro-inflammatory mediators generated in peripheral tissue communicate with the brain to modify behaviour [2], which aids our ability to fight and eliminate the pathogen. The communication pathways from the site of inflammation to the brain have been investigated in animal models and systemic challenge with lipopolysaccharide (LPS) or double stranded RNA (poly I:C) have been widely used to mimic aspects of bacterial and viral infection respectively [3, 4]. These studies have provided evidence that systemically generated inflammatory mediators signal to the brain via both neural and humoral routes, the latter signalling via the circumventricular organs or across the blood-brain barrier (BBB). Signalling into the brain via these routes evokes a response in the perivascular macrophages (PVMs) and microglia, which in turn synthesise diverse inflammatory mediators including cytokines, prostaglandins and nitric oxide [2, 5, 6]. Immune-to-brain communication also occurs in humans who show changes in mood and cognition following systemic inflammation or infection, which are associated with changes in activity in particular regions of the CNS [7-9]. While these changes are part of our normal homeostasis, it is increasingly evident that systemic inflammation has a detrimental effect in animals and also humans, that suffer from chronic neurodegeneration [10, 11]. We, and others, have shown that microglia become primed by on-going neuropathology in the brain, which increases their response towards subsequent inflammatory stimuli, including systemic inflammation [12, 13] Similar findings have been made in aged rodents [14, 15], where it has been shown that there is an exaggerated behavioural and innate immune response in the brainto systemic bacterial and viral infections, but the molecular mechanisms underlying the microglial priming under these conditions is far from understood.Humans and animals are rarely exposed to a single acute systemic inflammatory event: they rather encounter infectious pathogens that replicate in vivo or are exposed to low concentrations of LPS over a prolonged period of time. There is limited information on the impact of non-neurotrophic bacterial infections on the CNS and whether prolonged systemic inflammation will give rise to either a hyper-(priming) or hypo-(tolerance) innate immune response in the brain in response to a subsequent inflammatory stimulus.In this study we measured the levels of cytokines in the serum, spleen and brain as well as assessing sickness behaviour following a systemic bacterial infection using attenuated Salmonella typhimurium SL3261: we compared the effect to that of repeated LPS injections. We show that Salmonella typhimurium caused acute, transient behavioural changes and a robust peripheral immune response that peaks at day 7. Systemic inflammation resulted in a delayed increase in cytokine production in the brain and priming of microglia, which persisted up to four weeks post infection. These effects were not mimicked by repeated LPS challenges. It is well recognised that systemic bacterial and viral infections are significant contributors to morbidity in the elderly [16], and it has been suggested that primed microglia play a role in the increased clinical symptoms seen in patients with Alzheimer’s disease who have systemic inflammation or infections [11, 17]. We show here that systemic infection leads to prolonged cytokine synthesis in the brain and also priming of brain innate immune cells to a subsequent focal inflammatory challenge in the brain parenchyma

    Megophrys (Xenophrys) himalayana Mahony & Kamei & Teeling 2018, sp. nov.

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    Megophrys (Xenophrys) himalayana sp. nov. (Figures 20 & 21; Table 1) Holotype. Adult male (BNHS 6050 [field no. SDBDU 2009.1227]: Figures 20, & 21A, F & H), from Elephant village (27°4'56.52"N, 92°34'50.22"E, 370 m asl.), West Kameng district, Arunachal Pradesh state, Northeast India, collected by members of the Systematics Lab, University of Delhi on either 0 4 or 0 5 August 2009. Paratypes. Four adult males (BNHS 6051–6054 [field nos. SDBDU 2009.1206 – 1209]: Figure 21C, D, F & H), from Elephant village collected along with the holotype by members of the Systematics Lab, University of Delhi between 0 4 and 0 5 August 2009. Referred specimens. Adult male (SDBDU 2009.787: Figure 21E & G), and adult female (SDBDU 2009.750: Figure 21B & G), from Rengging village (28°8'32.52"N, 95°16'18.72"E, 410 m asl.), East Siang district, Arunachal Pradesh state, Northeast India, collected by Systematics Lab members between 24 and 25 July 2009. Holotype description (measurements in mm). Mature male (SVL 72.1) (Figures 20, & 21A, F & H). Head moderately large, as wide as long (HW 27.0, HL 26.9, IFE 13.3, IBE 21.4); snout bluntly pointed in dorsal view, obtusely protruding beyond mandible in lateral view, without rostral appendage (Figure 20C); loreal region acute, concave; canthus rostralis angular; dorsal surface of snout very slightly concave; eye diameter more than twice maximum diameter of visible portion of tympanum, slightly shorter than snout length (EL 9.0, TYD 4.0, SL 9.6); eye–tympanum distance (TYE 5.8) approximately two times diameter of visible portion of tympanum; tympanum oval-shaped, oblique, with upper border concealed by supratympanic ridge (Figure 20C); pupil vertically elliptical; nostril positioned laterally, closer to eye than to snout tip (EN 4.0, NS 5.6); internarial distance greater than eyelid width and narrowest point between upper eyelids (IN 8.7, UEW 7.8, IUE 7.8); pineal ocellus not visible externally; vomerine ridge present, medium sized, ovoid, moderately raised, orientated acutely, positioned between to slightly posterior to choanae, equidistant from choanae and each other; vomerine teeth short; maxillary teeth present; tongue not observed due to fixation of jaw and in interest of preventing potential damage to jaws by forcing open mouth wide enough for examination. Forelimbs long, thin (Figure 20A & B), forearm moderately enlarged relative to upper forelimb, and shorter than hand length (FAL 16.7, HAL 19.0); fingers long, narrow, without lateral fringes (Figure 20D), finger length formula IV 65% of trunk length; posterior edge of tongue weakly bifurcate on three examined specimens (SDBDU 2009.750, BNHS 6051, BNHS 6053); typically only upper 10–25% of tympanum concealed by supratympanic ridge; parietoscapular-sacral ridges vary considerably in configuration, i.e., “>–– – <”, or only V-shaped parietoscapular ridge present; coverage of dermal asperities varies mostly in density between individual males from Elephant Village, in comparison with holotype, however, male from Rengging Village (SDBDU 2009.787) has much less coverage of asperities, having white asperities mostly restricted to posterior dorsum and dorsal ridges; Rengging Village female (SDBDU 2009.750) has few white asperities on posterior dorsum and on dorsal surfaces of thighs; outer metacarpal tubercles not visible on some specimens; tubercle cover on flanks varies considerably, some with only sparse scattering of small tubercles, others with moderately dense cover of heterogeneous sized (large to small) tubercles (Figure 21 A–E); dorsal and ventral markings vary considerably between individuals (see Figure 21 which represent extremes in variation). Secondary sexual characters. Males: nuptial pads present, weakly raised, covered with black microasperities, covering most of dorsal surface of Finger I; nuptial pad on Finger II medium sized, oval, positioned on base of digit on inner dorsal side, extending onto base of proximal phalange; external vocal sac indistinct; moderately large internal vocal slits present on floor of mouth near rear of mandible on each side; forearms enlarged relative to upper forelimbs. Female: ova not pigmented; nuptial pads, vocal sac, vocal slits, enlarged forearms, all absent. Morphological comparison. Megophrys himalayana sp. nov. (adult males, N =7, adult female, N =1) differs from M. monticola and M. zhangi by its larger adult body size, male SVL 68.0– 73.5 mm, female SVL 83.9 mm (vs. male SVL 38.2–49.5 mm, N =17, female SVL 40.5–56.1 mm, N =6; male SVL 32.5–37.2 mm, N =3, respectively); differs from M. robusta by its smaller adult male size, SVL 68.0– 73.5 mm (vs. male SVL 73.5–83.1 mm, N =6), black dermal asperities on ventral surface of thighs and posterior abdomen of males absent (vs. of six adult males examined, asperities present on ventral surface of thighs of all, and on abdomen of five); differs from M. medogensis by its slightly larger adult male body size, SVL 68.0– 73.5 mm (vs. male SVL 57.2–68.0 mm, N =16), iris colour in life maroon to red (vs. light golden [Zhao et al. 2005; Li et al. 2010; Fei et al. 2010, 2012]). From MMC members, Megophrys himalayana sp. nov. differs from Megophrys flavipunctata sp. nov. by toes rounded, not flattened, lateral fringes absent (vs. toes dorsoventrally flattened, with or without narrow lateral dermal fringes), forearms of adult males moderately enlarged relative to upper arms (vs. not enlarged relative to upper arms); differs from Megophrys oreocrypta sp. nov. and M. major s.s. by dark spots associated with flank tubercles typically present (vs. absent), further from Megophrys oreocrypta sp. nov. by light portion of upper lip not extending beyond nostril (vs. light upper lip stripe extends anteriorly beyond nostril), further from M. major s.s. by webbing on Toe IV of males not extending beyond basal articulation, i.e., 4IV 4 (vs. webbing more extensive on males, i.e., 3.2IV3.2 to 3.6IV3.6), toe tips not expanded relative adjacent toe width (vs. expanded); from M. mangshanensis by larger adult body size, male SVL 68.0– 73.5 mm, female SVL 83.9 mm (vs. male SVL 62.5 mm, N =1, female SVL 73.0 mm, N =1). For comparisons with additional species covered in this study, refer to relevant morphological comparison sections. Systematic position. This taxon represents M. cf. major 5 (OTU 13) in the molecular analyses, and “ M. cf. major [4]” in Mahony et al. (2017). The systematic position of Megophrys himalayana sp. nov. within the MMC is currently unclear. Concatenated gene trees of mt+nuDNA or mtDNA only (Figures 2 & 4; Appendix I, Table 3; Appendix II, Figures 1, 2 & 5), and gene coalescence analysis of the unphased nuDNA-only dataset (Figure 5A; Appendix I, Table 3) placed this species as sister taxon to M. cf. major 4 (described as a new species, below), whereas, gene coalescence analysis of the phased nuDNA-only dataset (Figure 5B) placed this species as sister taxon to a clade comprising Megophrys flavipunctata sp. nov. and M. cf. major 4 (described as a new species, below). Refer to Appendix I, Table 6 for uncorrected p -distances for the 16S rRNA gene between Megophrys himalayana sp. nov. and other MMSG species. Etymology. The species epithet “ himalayana ” is a toponym in reference to the known distribution range of this species that is restricted to the southern Himalayas. Suggested common name: Himalayan Horned Frog. Distribution. The type series and referred specimens were collected from two widely separated localities in the state of Arunachal Pradesh, indicating an Indian distribution that ranges at least from East Siang district, west to West Kameng district, at low elevation (375–410 m asl.) (Figure 8A). A more extensive sampling is necessary to define the east-west limits of this species’ geographic range. Habitat and natural history. All specimens were collected after dusk. Animals were found typically perched on the rocky banks of small (~ 1–3 m wide), presumably temporary/seasonal, fast flowing mountain streams bordered by dense mature secondary/primary forest. This species probably favours smaller streams– –at the type locality specimens were collected from one of the small tributaries of the large Sessa stream (Figure 9E), but were not found on the banks of the Sessa stream itself. The two smallest male specimens, BNHS 6052 with no internal vocal slits and BNHS 6054 with very small internal vocal slits, had enlarged testes, well developed nuptial pads and enlarged forearms, indicating that males of this species begin reaching sexual maturity at around SVL 68.0– 68.5 mm. Although all males appeared to be in breeding condition, no vocalisations were heard at the collection localities. Furthermore, the female contained relatively under-developed ova in its ovaries indicative that the breeding season might begin sometime in late July or early August, towards the end of the monsoon season.Published as part of Mahony, Stephen, Kamei, Rachunliu G. & Teeling, Emma C., 2018, Cryptic diversity within the Megophrys major species group (Amphibia: Megophryidae) of the Asian Horned Frogs: Phylogenetic perspectives and a taxonomic revision of South Asian taxa, with descriptions of four new species, pp. 1-96 in Zootaxa 4523 (1) on pages 54-58, DOI: 10.11646/zootaxa.4523.1.1, http://zenodo.org/record/261020

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Megophrys (Xenophrys) periosa Mahony & Kamei & Teeling 2018, sp. nov.

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    Megophrys (Xenophrys) periosa sp. nov. (Figures 22 & 23; Table 1) Holotype. Adult male (BNHS 6055 [field no. SDBDU 2009.793]: Figures 22, & 23A & H), from Pangin town (28°12'33.96"N, 94°59'10.02"E, 450 m asl.), East Siang district, Arunachal Pradesh state, Northeast India, collected by members of the Systematics Lab, University of Delhi on 26 July 2009. Paratypes. Four adult males (BNHS 6057 [field no. SDBDU 2009.794]: Figure 23B; BNHS 6058–6060 [field nos. SDBDU 2009.1170 – 1172]: Figure 23H), collected along with the holotype by members of the Systematics Lab, University of Delhi on 26–28 July 2009; four adult males (BNHS 6061 [field no. SDBDU 2009.1243]: Figure 23E; BNHS 6062 [field no. SDBDU 2009.1244], BNHS 6063–6064 [field nos. SDBDU 2009.1265 – 1266]: Figure 23G), and one adult female (BNHS 6056 [field no. SDBDU 2009.1285]: Figure 23F), from the Sessa River, nearby Sessa village (27°6'4.02"N, 92°31'38.52"E, 1110 m asl.), West Kameng district, Arunachal Pradesh state, Northeast India, collected by members of the Systematics Lab, University of Delhi on 07–09 August 2009. Referred specimens. Two adult males (SDBDU 2009.1189: Figure 23D; SDBDU 2009.1190: Figure 23C), from Rigo Village (28°9'34.56"N, 94°47'19.38"E, 260 m asl.), Along town, West Siang district, Arunachal Pradesh state, Northeast India, collected by Systematics Lab members on 30 July 2009; one adult male (SDBDU 2009.1267), from the Sessa River, nearby Sessa village (27°6'4.02"N, 92°31'38.52"E, 1110 m asl.), West Kameng district, Arunachal Pradesh state, Northeast India, collected by members of the Systematics Lab, University of Delhi on 07–09 August 2009. Provisionally referred specimens (see Remarks). One juvenile male (SDBDU 2009.132), and two juvenile females (SDBDU 2009.133 & SDBDU 2009.134), from Pangkava ju (24°40'21.6"N, 94°28'19.86"E, 820 m asl.), Kangpat Khullen, Kamjong sub-division, Ukhrul district, Manipur state, Northeast India, collected by RGK and SDB on 21 May 2009; adult female (CAS 232938 ––tissue only), from Hepu Stream (25°5'25.2"N, 96°24'13.2"E), Hepu village, Moe Nyin township, Myitkyina district, Kachin state, northern Myanmar, collected by G.O.U. Wogan, J.A. Wilkinson, J.V. Vindum, H. Win, T. Thin [“Additional collectors: K.S. Lwin, A.K. Shein and H. Tun ”] on 14 May 2003. Holotype description (measurements in mm). Mature male (SVL 93.8) (Figures 22, & 23A & H). Head moderately large, wider than long (HW 35.0, HL 33.6, IFE 15.5, IBE 25.3); snout bluntly pointed in dorsal view, obtusely protruding beyond mandible in lateral view, without rostral appendage (Figure 22C); loreal region acute, concave; canthus rostralis angular; dorsal surface of snout very slightly concave; eye diameter twice maximum diameter of visible portion of tympanum, and shorter than snout length (EL 10.7, TYD 5.4, SL 11.7); eyetympanum distance (TYE 8.2) less than twice diameter of visible portion of tympanum; tympanum oval-shaped, oblique (Figure 22C), with upper ~15% concealed by supratympanic ridge; pupil vertically elliptical; nostril positioned laterally, closer to eye than to snout (EN 5.2, NS 7.1); internarial distance greater than eyelid width, and equal to narrowest point between upper eyelids (IN 10.5, UEW 8.7, IUE 10.5); pineal ocellus not visible externally; vomerine ridge present, medium sized, ovoid, moderately raised, orientated acutely, positioned between to slightly posterior to choanae, equidistant from choanae and each other; vomerine teeth short; maxillary teeth present; tongue not observed due to fixation of jaw and in interest of preventing potential damage to jaws by forcing open mouth wide enough for examination. Forelimbs long, thin (Figures 22A & B, & 23A), forearm moderately enlarged relative to upper forelimb, and shorter than hand length (FAL 20.6––left side; right side deformed; HAL 24.0); fingers long, narrow, without lateral fringes (Figure 22D), finger length formula IV –75% of the trunk length (Figure 23 A–F); typically only upper border of tympanum is concealed by supratympanic ridge, though up to ~25% of tympanum appears to be concealed on some specimens; parietoscapular-sacral ridge configuration varies considerably amongst individuals, i.e., “>- (”, “>–– |”, “>- <”, or only V-shaped parietoscapular ridge present; coverage of dermal asperities varies mostly in density between individual males in comparison with holotype, however, on some specimens both black (or brown) and white asperities were observed, may sparsely cover upper lips, loreal region, front of snout, posterior dorsal surface of upper eyelids, head, and dorsal surface of tibia-tarsus joints; asperities white on female, restricted to dorsal surface of body, sparse on middorsum, increasing in density posteriorly to above cloaca; outer metacarpal tubercles not visible on most specimens; tubercle cover on flanks varies considerably, some with only sparse scattering of small tubercles, others with moderately dense cover of heterogeneous (large to small) sized tubercles (Figure 23 A–F). Dorsal and ventral markings vary considerably between individuals (see Figure 23 which represent extremes in variation). Secondary sexual characters. Males: nuptial pads present, weakly raised, covered with brown/black microasperities on freshly collected specimens, covering most of dorsal surface of Finger I; nuptial pad on Finger II medium sized, oval, positioned on base of digit on inner dorsal side, extending almost to base of distal phalange; external vocal sac indistinct; large internal vocal slits present on floor of mouth near rear of mandible, on each side; forearms enlarged relative to upper forelimbs. Female: mature ova without pigmented poles; nuptial pads, vocal sac, vocal slits, enlarged forearms, all absent. Morphological comparison. Characters used for comparing Megophrys periosa sp. nov. with its congeners do not include those from the provisionally assigned referred specimens. Megophrys periosa sp. nov. (adult males, N =12, adult female, N =1) differs from M. medogensis, M. zhangi and M. monticola by its larger adult body size, male SVL 71.3–93.8 mm, female SVL 112.0 mm (vs. male SVL 57.2–68.0 mm, N =17; male SVL 32.5–37.2 mm, N =3; male SVL 38.2–49.5 mm, N =17, female SVL 40.5–56.1 mm, N =6, respectively); differs from M. robusta by absence of black dermal asperities on posterior abdomen of adult males (vs. usually present), Finger II<I in length, N =13 (vs. Finger I=II, N =10); differs from Megophrys flavipunctata sp. nov., Megophrys oreocrypta sp. nov., M. major s.s. and M. mangshanensis by absence of distinct white, cream or light coloured stripe along upper lips (vs. present); further differs from Megophrys flavipunctata sp. nov. and M. mangshanensis by its larger adult body size, male SVL 71.3–93.8 mm, female SVL 112.0 mm (vs. male SVL 56.9–68.4 mm, N =4, female SVL 68.0– 74.6 mm, N =3; male SVL 62.5 mm, N =1, female SVL 73 mm, N =1, respectively); further from M. major s.s. by dark spots associated with flank tubercles typically present (vs. absent), toe tips not expanded relative to adjacent toe width (vs. expanded); differs from Megophrys himalayana sp. nov. by its typically larger adult body size, male SVL 71.3–93.8 mm, female SVL 112.0 mm (vs. male SVL 68.0– 73.5 mm, N =7, female SVL 83.9 mm, N =1), typically smaller eye diameter to snout length ratio for males, ED/ES 76.6–91.5%, mean 84.3 ± 4.2% (vs. ED/ES 87.6–101.1%, N =7, mean 94.2 ± 4.6%). Systematic position. This taxon represents M. cf. major 4 (OTU 12) in the molecular analyses, and “ M. cf. major [5]” in Mahony et al. (2017). Megophrys periosa sp. nov. consistently formed a sister taxa relationship with two populations found east of the Brahmaputra River in Manipur and Myanmar referred to herein as Megophrys cf. periosa (M. cf. major 6/OTU 14 in molecular analyses). Uncorrected p -distances for the 16S rRNA gene between Megophrys periosa sp. nov. and M. cf. periosa was 1.6–2.0% (Appendix I, Table 6). The systematic position of this clade within the MMC was not fully resolved (see Systematic position section for Megophrys himalayana sp. nov. for further details), however most analyses placed this species as the sister taxon of Megophrys himalayana sp. nov. (Figures 2 & 4; Appendix I, Table 3; Appendix II, Figures 1, 2 & 5; Mahony et al. 2017). Refer to Appendix I, Table 6 for uncorrected p - distances for the 16S rRNA gene between Megophrys periosa sp. nov. and other MMSG species. Etymology. The species epithet “ periosa ” is a Latinised Greek adjective meaning “immense”, in reference to the very large size that this species attains, even compared to otherwise generally large species in the MMC. Suggested common name: Giant Himalayan Horned Frog. Distribution. Megophrys periosa sp. nov. is so far confirmed from three localities in the state of Arunachal Pradesh, Northeast India. The currently known distribution ranges from East Siang district, west through West Siang district, to at least West Kameng district, between 260 and 1110 m asl. (Figure 8A). An improved and more extensive sampling is necessary to define the east-west limits of this species’ geographic range. Specimens assigned here to Megophrys cf. periosa were collected from Ukhrul district (at 820 m asl.), Manipur state, Northeast India, and from Myitkyina district, Kachin state, northern Myanmar (Figure 8A). Habitat and natural history. All males were in breeding condition, and the female contained well-developed ova within her ovaries, indicative that the breeding season extends at least through late-July and early-August. All specimens were collected after dusk, typically perched on the rocky banks of small to large (1–15 m wide) moderately fast flowing mountain streams flowing through dense mature secondary/primary forest (e.g., Figure 9A & F). Males spaced themselves along the banks of the streams at least 10 m apart. Vocalisations typically consisted of a succession of a few notes followed by an extended silence, but were rarely heard. Healed injuries were observed on two specimens; the right hand of the holotype appears to have been badly dislocated or broken (Figure 22B & E). This large mature male had noticeably less well-developed nuptial pads than the other males, possibly as a result of lower overall fitness, although it otherwise appeared to be in good health. One other specimen (BNHS 6064) had a large swelling on Finger II on the right hand, the cause for which is unclear. Remarks. Specimens reported as M. lateralis and/or M. robusta by Borah and Bordoloi (2001), Bordoloi et al. (2000) and Sarkar and Ray (2006) from Arunachal Pradesh may apply to this species, and/or Megophrys himalayana sp. nov. The specimens reported in these studies should be re-examined to determine the correct identities. Populations provisionally assigned to this taxa (as M. cf. periosa) from eastern Manipur state, Northeast India and northern Myanmar, were found to be the sister taxon to Megophrys periosa sp. nov. (Mahony et al. 2017 [as M. cf. major [6]]; Figures 2, 4 & 5). Regardless of BPP results indicating that this lineage may represent a distinct species-level taxon (Appendix I, Table 5), we recommend that comparable series of adult specimens be studied to further determine the taxonomic status of this lineage. For now, it may provisionally be regarded as conspecific with Megophrys periosa sp. nov.Published as part of Mahony, Stephen, Kamei, Rachunliu G. & Teeling, Emma C., 2018, Cryptic diversity within the Megophrys major species group (Amphibia: Megophryidae) of the Asian Horned Frogs: Phylogenetic perspectives and a taxonomic revision of South Asian taxa, with descriptions of four new species, pp. 1-96 in Zootaxa 4523 (1) on pages 59-63, DOI: 10.11646/zootaxa.4523.1.1, http://zenodo.org/record/261020

    [Newspaper Clipping: Author Claims Evidence of Second JFK Assassin #1]

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    Newspaper article titled "Author Claims Evidence of Second JFK Assassin." The article states that author Richard J. Whalen concluded "that there is circumstantial evidence to support the theory of a second assassin in the shooting of President John F. Kennedy.

    Megophrys (Xenophrys) oreocrypta Mahony & Kamei & Teeling 2018, sp. nov.

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    Megophrys (Xenophrys) oreocrypta sp. nov. (Figures 18 & 19; Table 1) Holotype. One adult female (BNHS 6045 [field no. SDBDU 2009.1108]: Figures 18, & 19A & C), from Tura Peak Reserve Forest (25°30'29.4"N, 90°13'44.82"E, 640 m asl.), near Tura town, West Garo Hills district, Meghalaya state, Northeast India, collected by members of the Systematics Lab, University of Delhi on 20 June 2009. Paratypes. Four unsexed juveniles (BNHS 6046 – BNHS 6049 [field nos. SDBDU 2009.1104 – 1107]: Figure 19B, D, E & F), collected along with the holotype. Referred specimen. One unsexed juvenile (SDBDU 2008.1400; not measured), from Tura Peak Reserve Forest (25°30'40"N, 90°13'50"E, 510 m asl.), near Tura town, West Garo Hills district, Meghalaya state, Northeast India, collected by RGK on 13 May 2008; one juvenile (FMNH 74154 [previously ZSIC 18492]), from “Tura, Garo Hills, Assam ” (now West Garo Hills district, Meghalaya state), collected by S.W. Kemp, date unknown. Holotype description (measurements in mm). Mature female (SVL 94.9) (Figures 18, & 19A & C). Head moderately large, slightly wider than long (HW 35.9, HL 35.7, IFE 16.2, IBE 25.6); snout bluntly pointed in dorsal view, obtusely protruding beyond mandible in lateral view, without rostral appendage (Figure 18C); loreal region acute, concave; canthus rostralis angular; dorsal surface of snout concave; eye diameter almost twice as long as maximum diameter of visible portion of tympanum, and shorter than length of snout (EL 9.0, TYD 4.7, SL 11.8); eye–tympanum distance (TYE 8.2) longer than diameter of visible portion of tympanum; tympanum oval-shaped, slightly oblique (Figure 18C), with upper ~15% concealed by supratympanic ridge; pupil in life vertically elliptical; nostril positioned laterally, closer to eye than to snout (EN 6.0, NS 6.5); internarial distance greater than eyelid width, and slightly less than narrowest point between upper eyelids (IN 9.3, UEW 8.4, IUE 9.6); pineal ocellus not visible externally; vomerine ridges medium sized, ovoid, moderately raised, positioned between to slightly posterior to choanae, equidistant from each other and choanae; vomerine teeth small; maxillary teeth present; tongue moderately large, medial lingual process absent, posterior edge not observed due to fixation of jaw and in interest of preventing potential damage to jaws by forcing open mouth wide enough for examination. Forelimbs moderately long, thin (Figures 18A & B, & 19A & C), forearm not enlarged relative to upper forelimb, and shorter than hand length (FAL 21.5, HAL 23.3); fingers moderately long, narrow, without lateral fringes (Figure 18D), finger length formula IV <II<I<III (FIL 12.4, FIIL 10.7, FIIIL 15.4, FIVL 10.1); interdigital webbing, subarticular, supernumerary and metacarpal tubercles absent; thenar tubercles weak; finger tips rounded, slightly expanded relative to digit widths (FIIIW 1.8, FIIIDW 2.0), with subcircular pads, terminal grooves on pads absent. Hindlimbs long, thin (Figures 18A & B, & 19A & C); thighs shorter than shanks, longer than feet (TL 44.8, SHL 48.0, FOL 41.6); toes long, dorsoventrally flattened, without lateral fringes (Figure 18E), relative toe lengths I<II<V<III <IV; toe tips rounded, moderately expanded relative to digit width (TIVW 2.0, TIVDW 2.5) with distinct longitudinally oval-shaped pads, terminal grooves on pads absent; webbing basal, to distal edge of metatarsal on Toe IV (3 III 2.5– 4 IV 4.2–2.5V); inner metatarsal tubercle very weakly developed; subarticular, supernumerary and outer metatarsal tubercles absent; ridge of callous tissue absent on ventral surface of toes. Skin of dorsal surfaces of body, limbs, and dorsal and lateral surfaces of head primarily smooth; tympanum smooth, slightly concave, with borders slightly raised; outer edge of upper eyelids with a weak medial bump; supratympanic ridges narrow anteriorly gradually expanding beyond posterior edge of tympanum to become moderately enlarged and glandular, extending from posterior edge of orbits, through upper portion of tympanum, curving down abruptly at posterior tympanum border, terminating above forelimb insertion; flanks weakly granular with medium to large scattered pustular tubercles; dorsolateral ridges thin, weakly defined, extending from behind supratympanic ridges, almost entire length of trunk; weakly developed V-shaped parietoscapular ridge present, sacral ridges absent; ventral surfaces of head, body and limbs smooth; pectoral glands small, weakly raised, positioned on chest at mid-level of forelimb insertion; femoral glands large, flat, on posterior surface of thighs, slightly closer to knees than to cloaca; dermal asperities absent from all surfaces. Colouration: In preservative (Figure 18): Dorsal and lateral surfaces of body, and dorsal surface of head primarily mid brown; light-edged, dark brown incomplete triangular marking between eyes; faint dark brown blotch on centre of dorsum; tubercles on flanks primarily creamish-white; lateral surfaces of head below supratympanic ridges and canthus rostralis dark brown with cream-white stripe on upper lip, extending from anterior to nostril to rear of jaw; dorsal and lateral surfaces of forelimbs and hindlimbs primarily brown; two or three dark brown blotches on dorsolateral surface of forearms; dorsal surface of fingers with dark brown blotches; dorsal surfaces of hindlimbs with faint transverse crossbars; throat pale brown with brown and creamish-white spots and blotches along edge of gular region, light-edged wide light brown stripe extending from posterior edge of mandible onto base of forearms; chest light brown; abdomen, ventral surfaces of forelimbs and thighs plain creamish-white, ventral surface of shanks grey; dark brown longitudinal stripe ventrolaterally on both sides of abdomen; area surrounding vent and posterior surfaces of thighs dark brown; ventral surfaces of tarsi and feet dark greyish-brown; hands ventrally pale greyish-brown; pectoral and femoral glands creamish-white. In life (Figure 19A & C): Dorsal surfaces of head, body and limbs orangish-brown; upper lip stripe pale greyish-brown, darker anteriorly, fading posteriorly; posterior flanks and groin region with yellow hue; ventral surface of throat and chest primarily pale grey with dark orange speckling, speckling more dense on lateral stripes of throat, and ventrolaterally on anterior abdomen; abdomen and ventral surfaces of thighs white. Variation. See Table 1 for morphometric variation within the examined specimen series, consisting of an adult female, and five juveniles. All juveniles have head width less than head length; FMNH 74154 has finger length formula IV<I=II<III; posterior edge of tongue (examined on FMNH 74154 and BNHS 6046) distinctly bifurcate posteriorly; up to ~20% of upper portion of tympanum appears to be concealed by supratympanic ridge; dorsal surfaces of head and body of juveniles weakly granular; light upper lip stripe not visible on specimens smaller than SVL 41.0 mm (e.g., Figure 19E & F); BNHS 6046 has distinct brown X-shaped marking on dorsum; BNHS 6046 and BNHS 6047 have small white asperities along dorsal ridges (e.g., Figure 19E). See Figure 19C and 19D for ventral colouration variation between holotype and juvenile specimens. Secondary sexual characters. Males currently unknown. Morphological comparison. Megophrys oreocrypta sp. nov. (adult female, N =1) differs from M. monticola by its larger adult female body size, SVL 94.9 mm (vs. female SVL 40.5–56.1 mm, N =6); differs from M. robusta, M. medogensis and M. zhangi by absence of distinct dark brown vertical bar extending from lower orbital edge to edge of upper lip (vs. present) and presence of a distinctly lighter continuous upper lip stripe (vs. upper lip stripe absent). From other members of M. major species complex, it can be distinguished from Megophrys flavipunctata sp. nov. and M. mangshanensis by its larger adult female body size, SVL 94.9 mm (vs. female SVL 68.0– 74.6 mm, N =3; female SVL 73.0 mm, N =1, respectively), upper lip stripe extends anteriorly beyond nostril, N =4 [includes subadults] (vs. stripe terminates at, or posterior to nostril); differs from M. major s.s. by larger tympanum diameter/ eye diameter ratio, TYD/EL 52.2% (vs. female TYD/EL 40.0–41.2%, N =3), upper lip stripe extends anteriorly beyond nostril, N =4 [includes subadults] (vs. stripe terminates at, or posterior to nostril on all examined specimens, N= 15), pair of distinctly enlarged glands adjacent to cloaca absent, N =2 (vs. present, N =15). Systematic position. This taxon represents M. cf. major 1 in the molecular analyses (discussed as OTU 7), and in Mahony et al. (2017). The systematic position of Megophrys oreocrypta sp. nov. within the MMC clade is not fully resolved. It has consistently been found to be a member of the western clade of the MMC, and the sister taxon to M. major s.s. across all multigene analyses except the ML analysis of Dataset I (Appendix II, Figure 6), however, the relationship of this sister taxa clade with other members of the MMC is not clear when molecular data for the MMSG was subjected to a variety of phylogenetic techniques (Figures 2–5; Appendix I, Table 3; Appendix II, Figures 1, 2, 5 & 6). Refer to Appendix I, Table 6 for uncorrected p -distances for the 16S rRNA gene between Megophrys oreocrypta sp. nov. and other MMSG species. Etymology. The specific epithet “ oreocrypta ” is an adjective derived from the Latinised Greek words óros meaning “mountain” and kryptos meaning “hidden” or “secret”, in reference to the difficulty of finding adults of this species despite making several field trips to the Tura Peak Reserve Forest during 2008, 2009 and 2011. Suggested common name: Garo White-lipped Horned Frog. Sangma and Saikia (2015) provide the local Garo (language) name “Diplok Nakma” for this species. Distribution. Megophrys oreocrypta sp. nov. is currently known only from the southern slopes of the Tura Peak Reserve Forest (510–640 m asl.), in the West Garo Hills district of Meghalaya state (Figure 8A). Sangma and Saikia (2015) collected this species from slightly lower elevation on Tura Peak (437 m asl.) at Rengsangrap waterfall. It is likely that this species will be found throughout the adjoining Nokrek National Park and Biosphere Reserve, however its eastern distribution limits and altitudinal range are yet to be determined. Habitat and natural history. The habitat at the collection locality for this species consisted primarily of tropical lowland forest. The adult female holotype was collected after dusk, from the banks of one of the major streams flowing west towards Tura town. Juveniles were all collected after sunset on forest trails within ~ 20 m from the nearest large stream. The biology of this species remains unknown; no adult males have been heard calling from streams that were surveyed and the ovaries of the holotype are empty. Sangma and Saikia (2015) reported observing two (or five, according to their table 1) individuals of this species (as Xenophrys glandulosa) at the type locality, from among leaf litter and under moist rocks in the forest. Remarks. A report of M. robusta by Dutta (1997) from the Garo Hills is presumably based on Megophrys oreocrypta sp. nov. ( see “Remarks” for M. robusta). Smith (1929) reported M. major from Tura possibly based on the specimen collected by W. Kemp (FMNH 74154 [originally ZSIC 18492]), which we herein verify to represent Megophrys oreocrypta sp. nov. Sangma and Saikia (2015) provided a photograph (plate 4a) of a preserved specimen collected from the type locality, Tura Peak, which they referred to as Megophrys glandulosa. This specimen appears to represent Megophrys oreocrypta sp. nov. based on the presence of a white upper lip stripe that clearly extends anteriorly beyond the nostril.Published as part of Mahony, Stephen, Kamei, Rachunliu G. & Teeling, Emma C., 2018, Cryptic diversity within the Megophrys major species group (Amphibia: Megophryidae) of the Asian Horned Frogs: Phylogenetic perspectives and a taxonomic revision of South Asian taxa, with descriptions of four new species, pp. 1-96 in Zootaxa 4523 (1) on pages 50-54, DOI: 10.11646/zootaxa.4523.1.1, http://zenodo.org/record/261020

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