Sex Chromosome Turnover in Bent-Toed Geckos (\u3cem\u3eCyrtodactylus\u3c/em\u3e)

Lizards and snakes (squamates) are known for their varied sex determining systems, and gecko lizards are especially diverse, having evolved sex chromosomes independently multiple times. While sex chromosomes frequently turnover among gecko genera, intrageneric turnovers are known only from Gekko and Hemidactylus. Here, we used RADseq to identify sex-specific markers in two species of Burmese bent-toed geckos. We uncovered XX/XY sex chromosomes in Cyrtodactylus chaunghanakwaensis and ZZ/ZW sex chromosomes in Cyrtodactylus pharbaungensis. This is the third instance of intrageneric turnover of sex chromosomes in geckos. Additionally, Cyrtodactylus are closely related to another genus with intrageneric turnover, Hemidactylus. Together, these data suggest that sex chromosome turnover may be common in this clade, setting them apart as exceptionally diverse in a group already known for diverse sex determination systems

COVID-19 and civil unrest undoing steady gains in karst conservation and herpetological research in Myanmar, and an impediment to progress

The COVID-19 pandemic and political turmoil in Myanmar has dealt a severe blow to the country’s progress in herpetological research and the protection of limestone habitats. Both afflictions have reversed much of the scientific and conservation gains made in the past decade, and continue to hinder exploratory surveys and continued monitoring of threatened karst ecosystems. There is an urgent need to resume field studies and conservation efforts as soon as possible and continue enhancing the capacity of local scientific and technical staff in Myanmar

The biogeography of bent-toed geckos, Cyrtodactylus (Squamata: Gekkonidae)

The gekkonid genus Cyrtodactylus is the third largest vertebrate genus on the planet with well over 300 species that range across at least eight biogeographic regions from South Asia to Melanesia. The ecological and morphological plasticity within the genus, has contributed to its ability to disperse across ephemeral seaways, river systems, basins, land bridges, and mountain ranges—followed by in situ diversification within specific geographic areas. Ancestral ranges were reconstructed on a mitochondrial phylogeny with 346 described and undescribed species from which it was inferred that Cyrtodactylus evolved in a proto-Himalaya region during the early Eocene. From there, it dispersed to what is currently Indoburma and Indochina during the mid-Eocene— the latter becoming the first major center of origin for the remainder of the genus that seeded dispersals to the Indian subcontinent, Papua, and Sundaland. Sundaland became a second major center of radiation during the Oligocene and gave rise to a large number of species that radiated further within Sundaland and dispersed to Wallacea, the Philippines, and back to Indochina. One Papuan lineage dispersed west to recolonize and radiate in Sundaland. Currently, Indochina and Sundaland still harbor the vast majority of species of Cyrtodactylus

PATH-38. ROSETTE-FORMING GLIONEURONAL TUMOR IS DEFINED BY FGFR1 ACTIVATING ALTERATIONS WITH FREQUENT ACCOMPANYING PI3K AND MAPK PATHWAY MUTATIONS

Abstract BACKGROUND Rosette-forming glioneuronal tumor (RGNT) is an uncommon CNS tumor originally described in the fourth ventricle characterized by a low-grade glial neoplasm admixed with a rosette-forming neurocytic component. METHODS We reviewed clinicopathologic features of 42 patients with RGNT. Targeted next-generation sequencing was performed, and genome-wide methylation profiling is underway. RESULTS The 20 male and 22 female patients had a mean age of 25 years (range 3–47) at time of diagnosis. Tumors were located within or adjacent to the lateral ventricle (n=16), fourth ventricle (15), third ventricle (9), and spinal cord (2). All 31 tumors assessed to date contained FGFR1 activating alterations, either in-frame gene fusion, kinase domain tandem duplication, or hotspot missense mutation in the kinase domain (p.N546 or p.K656). While 7 of these 31 tumors harbored FGFR1 alterations as the solitary pathogenic event, 24 contained additional pathogenic alterations within PI3-kinase or MAP kinase pathway genes: 5 with additional PIK3CA and NF1 mutations, 4 with PIK3CA mutation, 3 with PIK3R1 mutation (one of which also contained focal RAF1 amplification), 5 with PTPN11 mutation (one with additional PIK3R1 mutation), and 2 with NF1 deletion. The other 5 cases demonstrated anaplastic features including hypercellularity and increased mitotic activity. Among these anaplastic cases, 3 harbored inactivating ATRX mutations and two harbored CDKN2A homozygous deletion, in addition to the FGFR1 alterations plus other PI3-kinase and MAP kinase gene mutations seen in those RGNT without anaplasia. CONCLUSION Independent of ventricular location, RGNT is defined by FGFR1 activating mutations or rearrangements, which are frequently accompanied by mutations involving PIK3CA, PIK3R1, PTPN11, NF1, and KRAS. Whereas pilocytic astrocytoma and ganglioglioma are characterized by solitary activating MAP kinase pathway alterations (e.g. BRAF fusion or mutation), RGNT are genetically more complex with dual PI3K-Akt-mTOR and Ras-Raf-MAPK pathway activation. Rare anaplastic examples may show additional ATRX and/or CDKN2A inactivation

The taxonomy and phylogeny of the Cyrtodactylus brevipalmatus group (Squamata: Gekkonidae) with emphasis on C. interdigitalis and C. ngati

Abstract Convergent morphological specializations for an arboreal lifestyle in most species of the Cyrtodactylus brevipalmatus group have been a confounding factor for establishing a stable taxonomy among its species. Recent references to C. interdigitalis from throughout Thailand and Laos were made without comparisons to the type material from Tham Yai Nam Nao, Nam Nao National Park, Phetchabun Province, Thailand, but instead, were based on general morphological similarity and distribution. The taxonomy of C. interdigitalis is stabilized here by comparing the paratypes to other specimens from Thailand and Laos and recovering their phylogenetic relationships based on newly acquired genetic data, including those from the type locality. The phylogeny recovered all specimens outside the type locality to be either C. ngati from Vietnam or new species closely related to C. ngati. Cyrtodactylus interdigitalis is shown here to be a range-restricted upland endemic on the Phetchabun massif of northern Thailand. The phylogeny also indicates that C. ngati extends hundreds of kilometers farther south into northern Thailand and central Laos. We hypothesize that the significant morphological divergence in body shape of the types of C. ngati, compared to that of the Lao and Thai populations, may be due to local adaptions for utilizing karst (C. ngati) rather than vegetation (Lao and Thai populations). Additionally, phylogenetic and multivariate analyses identified a potentially new species from Phu Hin Rong Kla National Park, Phitsanulok Province, in northern Thailand and another from the Khlong Naka Wildlife Sanctuary, Ranong Province, in southern Thailand. A series of newly examined specimens from Kaeng Krachan National Park, Phetchaburi Province, Thailand represents a possible ~82 km range extension to the southeast of C. rukhadeva. This research continues to underscore the high diversity of range-restricted upland endemics in Thailand and the importance of examining type material (if possible) in the context of a phylogeny so as to construct proper taxonomies that reveal, rather than obscure, diversity

Brain-derived neurotrophic factor prevents dendritic retraction of adult mouse retinal ganglion cells

We used cultured adult mouse retinae as a model system to follow and quantify the retraction of dendrites using diolistic labelling of retinal ganglion cells (RGCs) following explantation. Cell death was monitored in parallel by nuclear staining as ‘labelling’ with RGC and apoptotic markers was inconsistent and exceedingly difficult to quantify reliably. Nuclear staining allowed us to delineate a lengthy time window during which dendrite retraction can be monitored in the absence of RGC death. The addition of brain-derived neurotrophic factor (BDNF) produced a marked reduction in dendritic degeneration, even when application was delayed for 3 days after retinal explantation. These results suggest that the delayed addition of trophic factors may be functionally beneficial before the loss of cell bodies in the course of conditions such as glaucoma

A phylogenetic taxonomy of the Cyrtodactylus peguensis group (Reptilia: Squamata: Gekkonidae) with descriptions of two new species from Myanmar

A phylogenetic taxonomy of species in the Cyrtodactylus peguensis group from the Ayeyarwady Basin of Myanmar is constructed based on color pattern, morphology, and molecular systematic analyses using the mitochondrial gene NADH dehydrogenase subunit 2. Newly collected samples from the type locality of C. peguensis and other localities indicate that this clade is endemic to central Myanmar and contains at least seven species, four of which are undescribed. Three species, including C. peguensis occur in the low hills of the Bago Yoma Range within the central portion of the Ayeyarwady Basin. Two of these, C. myintkyawthurai sp. nov. from the northern and central Bago Yoma and C. meersi sp. nov. which is syntopic with C. peguensis in the southern Bago Yoma are described herein. As more lowland hilly areas bordering, and within the Ayeyarwady Basin are surveyed, more new species of this group are likely to be discovered. These discoveries continue the recent surge of descriptions of new species of Cyrtodactylus that are being discovered in Myanmar

Physiotherapy versus placebo or no intervention in Parkinson's disease

Background: Despite medical therapies and surgical interventions for Parkinson's disease (PD), patients develop progressive disability. Physiotherapy aims to maximise functional ability and minimise secondary complications through movement rehabilitation within a context of education and support for the whole person. The overall aim is to optimise independence, safety, and well-being, thereby enhancing quality of life.  Objectives: To assess the effectiveness of physiotherapy intervention compared with no intervention in patients with PD.  Search methods: We identified relevant trials by conducting electronic searches of numerous literature databases (e.g. MEDLINE, EMBASE) and trial registers, and by handsearching major journals, abstract books, conference proceedings, and reference lists of retrieved publications. The literature search included trials published up to the end of January 2012.  Selection criteria: Randomised controlled trials of physiotherapy intervention versus no physiotherapy intervention in patients with PD.  Data collection and analysis: Two review authors independently extracted data from each article. We used standard meta-analysis methods to assess the effectiveness of physiotherapy intervention compared with no physiotherapy intervention. Trials were classified into the following intervention comparisons: general physiotherapy, exercise, treadmill training, cueing, dance, and martial arts. We used tests for heterogeneity to assess for differences in treatment effect across these different physiotherapy interventions.  Main results: We identified 39 trials with 1827 participants. We considered the trials to be at a mixed risk of bias as the result of unreported allocation concealment and probable detection bias. Compared with no intervention, physiotherapy significantly improved the gait outcomes of speed (mean difference 0.04 m/s, 95% confidence interval (CI) 0.02 to 0.06, P = 0.0002); two- or six-minute walk test (13.37 m, 95% CI 0.55 to 26.20, P = 0.04) and Freezing of Gait questionnaire (-1.41, 95% CI -2.63 to -0.19, P = 0.02); functional mobility and balance outcomes of Timed Up & Go test (-0.63 s, 95% CI -1.05 to -0.21, P = 0.003), Functional Reach Test (2.16 cm, 95% CI 0.89 to 3.43, P = 0.0008), and Berg Balance Scale (3.71 points, 95% CI 2.30 to 5.11, P < 0.00001); and clinician-rated disability using the Unified Parkinson’s Disease Rating Scale (UPDRS) (total -6.15 points, 95% CI-8.57 to -3.73, P < 0.00001; activities of daily living: -1.36, 95% CI -2.41 to -0.30, P = 0.01; and motor: -5.01, 95% CI -6.30 to -3.72, P < 0.00001). No difference between arms was noted in falls (Falls Efficacy Scale: -1.91 points, 95% CI -4.76 to 0.94, P = 0.19) or patient-rated quality of life (PDQ-39 Summary Index: -0.38 points, 95% CI -2.58 to 1.81, P = 0.73). One study reported that adverse events were rare; no other studies reported data on this outcome. Indirect comparisons of the different physiotherapy interventions revealed no evidence that the treatment effect differed across physiotherapy interventions for any of the outcomes assessed.  Authors' conclusions: Benefit for physiotherapy was found in most outcomes over the short term (i.e. < 3 months) but was significant only for speed, two- or six-minute walk test, Freezing of Gait questionnaire, Timed Up & Go, Functional Reach Test, Berg Balance Scale, and clinician-rated UPDRS. Most of the observed differences between treatments were small. However, for some outcomes (e.g. speed, Berg Balance Scale, UPDRS), the differences observed were at, or approaching, what are considered minimal clinically important changes. These benefits should be interpreted with caution because the quality of most of the included trials was not high. Variation in measurements of outcome between studies meant that our analyses include a small proportion of the participants recruited.  This review illustrates that a wide range of approaches are employed by physiotherapists to treat patients with PD. However, no evidence of differences in treatment effect was noted between the different types of physiotherapy interventions being used, although this was based on indirect comparisons. A consensus menu of 'best practice' physiotherapy is needed, as are large, well-designed randomised controlled trials undertaken to demonstrate the longer-term efficacy and cost-effectiveness of 'best practice' physiotherapy in PD

Phylogenetic and multivariate analyses of Gekko smithii Gray, 1842 recover a new species from Peninsular Malaysia and support the resurrection of G. albomaculatus (Giebel, 1861) from Sumatra

An integrative taxonomic analysis of Sundaic populations of Gekko smithii from the Thai-Malaya Peninsula, Sumatra, and Borneo recovered four deeply divergent mitochondrial lineages that are separated by major geographic barriers (mountains and seaways). Furthermore, they bear a number of concordant statistically significant differences in meristic and morphometric features, morphospatial separation in multivariate space, and discrete differences in color pattern. Gekko smithii sensu stricto is restricted to southern Thailand south of the Isthmus of Kra and Peninsular Malaysia west of the Banjaran (mountain range) Titiwangsa, being that the type locality is on Penang Island, Penang. Gekko hulk sp. nov. is a new species from extreme southern Thailand and Peninsular Malaysia east of the Banjaran Titiwangsa and five east coast islands—the type locality being Pulau (island) Tioman, Pahang. Gekko cf. albofasciolatus is tentatively used to include Bornean populations west of the Iran Mountains in Sabah and Sarawak which, in the absence of molecular data, cannot unequivocally be separated morphologically from G. albofasciolatus from the type locality at Banjarmasin, Kalimantan, Indonesia east of the Iran Mountains. In the absence of molecular data, G. albomaculatus is resurrected to include mainland Sumatran, Nias Island, and Banyak Islands populations which, based on their morphology, cannot be separated from descriptions of G. albomaculatus from the type locality of Bangka Island, 15 km off the southeast coast of mainland Sumatra. Further integrative analyses of all Sumatran and Bornean populations are currently underway as well as the enigmatic Wallacean populations from Sulawesi. Data are presented that strongly suggest all references to G. smithii from Java stem from a 151 year-old misidentification of a specimen of G. gecko of unknown provenance. Additionally, there are no vouchered records of G. smithii from Myanmar. The phylogeographic patterns of Sundaic populations of the G. smithii complex are concordant with those of a plethora of other Sundaic lineages

Alcohol-Induced Blackout

For a long time, alcohol was thought to exert a general depressant effect on the central nervous system (CNS). However, currently the consensus is that specific regions of the brain are selectively vulnerable to the acute effects of alcohol. An alcohol-induced blackout is the classic example; the subject is temporarily unable to form new long-term memories while relatively maintaining other skills such as talking or even driving. A recent study showed that alcohol can cause retrograde memory impairment, that is, blackouts due to retrieval impairments as well as those due to deficits in encoding. Alcoholic blackouts may be complete (en bloc) or partial (fragmentary) depending on severity of memory impairment. In fragmentary blackouts, cueing often aids recall. Memory impairment during acute intoxication involves dysfunction of episodic memory, a type of memory encoded with spatial and social context. Recent studies have shown that there are multiple memory systems supported by discrete brain regions, and the acute effects of alcohol on learning and memory may result from alteration of the hippocampus and related structures on a cellular level. A rapid increase in blood alcohol concentration (BAC) is most consistently associated with the likelihood of a blackout. However, not all subjects experience blackouts, implying that genetic factors play a role in determining CNS vulnerability to the effects of alcohol. This factor may predispose an individual to alcoholism, as altered memory function during intoxication may affect an individual’s alcohol expectancy; one may perceive positive aspects of intoxication while unintentionally ignoring the negative aspects. Extensive research on memory and learning as well as findings related to the acute effects of alcohol on the brain may elucidate the mechanisms and impact associated with the alcohol-induced blackout